CN117835978A - Pharmaceutical combinations comprising TEAD inhibitors and their use for cancer treatment - Google Patents

Pharmaceutical combinations comprising TEAD inhibitors and their use for cancer treatment Download PDF

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Publication number
CN117835978A
CN117835978A CN202280057427.8A CN202280057427A CN117835978A CN 117835978 A CN117835978 A CN 117835978A CN 202280057427 A CN202280057427 A CN 202280057427A CN 117835978 A CN117835978 A CN 117835978A
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Prior art keywords
inhibitor
pharmaceutically acceptable
acceptable salt
tead
kras
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E·沙波
L·莱皮奇尔-桑斯雷格雷
T·施梅尔茨勒
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Novartis AG
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Novartis AG
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Priority claimed from PCT/IB2022/058104 external-priority patent/WO2023031781A1/en
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Abstract

The present invention relates to a pharmaceutical combination comprising a TEAD inhibitor in combination with a first therapeutically active agent and optionally a second therapeutically active agent. The invention also relates to methods of treating cancer involving administering to a subject in need thereof a combination of a TEAD inhibitor and a first therapeutically active agent and optionally a second therapeutically active agent.

Description

Pharmaceutical combinations comprising TEAD inhibitors and their use for cancer treatment
Technical Field
The present invention relates to a pharmaceutical combination comprising a TEAD inhibitor in combination with a first therapeutically active agent and optionally a second therapeutically active agent. The invention also relates to methods of treating cancer involving administering to a subject in need thereof a combination of a TEAD inhibitor and a first therapeutically active agent and optionally a second therapeutically active agent.
Background
The advent of targeted therapies for cancer has prolonged the life of patients with various malignant tumors and helped to understand the complexity of the tumor by studying the mechanism of drug resistance. The fact that clinical responses to targeted agents are often incomplete and/or transient is caused by a number of factors, which can be broadly divided into two categories: preventing optimal drug administration and thus limiting toxicity of target engagement (Brana and Siu2012; chapman, solit et al 2014), and the ability of cancer to adapt to disturbances and maintain its proliferative potential (Druker 2008;Chandarlapaty 2012;Doebele,Pilling et al 2012; duncan, whittle et al 2012; katayama, shaw et al 2012; lito, rosen et al 2013; sullivan and Flaherty 2013; solit and Rosen 2014). Combinations of drugs can address these factors by improving overall efficacy and simultaneously targeting tumor robustness and complexity to counteract drug resistance (Robert, karasizwska et al 2015; turner, ro et al 2015). It is not clear how many drugs are needed and which processes need to be targeted in combination to overcome a particular type of cancer. It has almost been determined that inhibition of different pathways or drivers is required, and that two or more drugs are likely to be required (Bozic, reiter et al 2013).
Despite the variety of treatment options for patients with a particular type of cancer, there remains a need for effective and safe combination therapies that can be administered to treat cancer.
Disclosure of Invention
It is an object of the present invention to provide a medicament to improve the treatment of cancer, in particular by inhibiting cell growth (proliferation) and/or inducing apoptosis (cell death). It is an object of the present invention to find new combination therapies which selectively synergistically enhance the inhibition of proliferation and/or the induction of apoptosis.
Surprisingly, it has been found, as demonstrated in the examples, that the following pharmaceutical combination is capable of synergistically simultaneously inhibiting proliferation and/or inducing apoptosis in cancer, the pharmaceutical combination comprising: i) TEAD inhibitors, ii) a first additional therapeutically active agent, and optionally iii) a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
Thus, according to a first aspect of the present invention there is thus provided a method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a TEAD inhibitor in combination with a first additional therapeutically active agent and optionally a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
According to a second aspect of the present invention there is thus provided a TEAD inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a first additional therapeutically active agent and optionally a second therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
According to a third aspect of the present invention there is thus provided a pharmaceutical combination comprising: i) TEAD inhibitors, ii) a first additional therapeutically active agent, and optionally iii) a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
According to a fourth aspect of the present invention there is thus provided a cMET inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a fifth aspect of the present invention there is thus provided an SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a sixth aspect of the present invention there is thus provided a MEK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a seventh aspect of the present invention there is thus provided an ERK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to an eighth aspect of the present invention there is thus provided a Raf inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a ninth aspect of the present invention there is thus provided an EGFR inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a tenth aspect of the present invention there is thus provided a PI3K inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to an eleventh aspect of the present invention there is thus provided an MDM2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
According to a twelfth aspect of the present invention there is thus provided a CDK4/6 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Drawings
Fig. 1: female nude mice bearing H2122 or 2094-HX subcutaneous xenograft lung tumors were treated daily orally (once daily (QD)) with compound a (4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide), compound C (1- {6- [ (4M) -4- (5-chloro-6-methyl-1H-indazol-4-yl) -5-methyl-3- (1-methyl-1H-indazol-5-yl) -1H-pyrazol-1-yl ] -2-azaspiro [3.3] heptan-2-yl } prop-2-en-1-one), AMG510 (also known as sotoracicb), or a combination, or vehicle. Values are mean ± SEM (standard error of mean); sample size (n=4 to 7 mice/group). Tumor volume is expressed as a percent change from the measurement on day 0 of treatment. Left panel, therapeutic effect results for H2122 xenograft model. Diamonds represent the results of the combination of compound A (220 mg/kg, qd) with compound C (100 mg/kg, qd). Right panel, curative effect results for xenograft (PDX) human lung model of 2094-HX patient origin. Treatment was stopped on study day 44, and tumor regrowth was observed in animals treated with a single agent after treatment was stopped compared to animals treated with the combination.
Fig. 2: female nude mice carrying 9 different colorectal cancer (CRC) subcutaneous PDX tumors were treated with the agents shown in the oral legend. Using the Mouse Clinical Trial (MCT) mode, n=2 for untreated, n=1 for each treatment. Left diagram: the reduction in tumor growth is shown using the volume non-doubling parameter, expressed as a percentage of all mouse values. Right figure: values are mean ± SEM; the percentage of the mean value of the optimal Tumor Volume (TV) change from baseline is shown.
Fig. 3: female nude mice bearing Lu99 lung subcutaneous xenograft tumors or ACC-MESO1 mesothelioma subcutaneous xenograft tumors were treated with compound a or compound B (2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide), TNO155 twice daily, or a combination, or vehicle control, shown in the daily oral (QD) legend. Values are mean ± SEM; sample size (n=5 to 9 mice/group). Tumor volumes are shown in the upper graph. The percentage change in body weight from baseline is shown in the lower graph.
Fig. 4: female nude mice bearing Lu99 lung subcutaneous xenograft tumors were treated with a single agent or combination of agents as shown in the oral legend. For compound a or compound B, the treatment was daily (QD) administration, for compound C, the treatment was daily administration, and for TNO155, the treatment was twice daily administration. Values are mean ± SEM; sample size (n=6 mice/group). Tumor volumes are shown on the left hand graph. The percentage change in body weight from baseline is shown in the right graph.
Fig. 5: female nude mice carrying Lu99 or 2094-HX lung subcutaneous xenograft tumors were treated with a single agent or combination of agents as shown in the oral legend. Values are mean ± SEM; sample size (n=4 to 6 mice/group). Tumor volumes are shown on the left hand graph. The percentage change in body weight from baseline is shown in the right graph.
Fig. 6: female nude mice bearing subcutaneous xenograft tumors were treated with a single agent or combination of agents as shown in the oral legend. A) Evaluation of antitumor efficacy and tolerability in NCI-H2052 mesothelioma subcutaneous xenograft model. Values are mean ± SEM; sample size (n=6 mice/group). B) Evaluation of anti-tumor efficacy and tolerability for 2094-HX lung subcutaneous xenograft model. Values are mean ± SEM; sample size (n=5-6 mice/group). C) MCT was performed with 23 PDAC PDX models, n=1-2 for each model and treatment. The reduction in tumor growth, expressed as a percentage of the mouse population, was shown using the volume non-doubling parameter.
Fig. 7: female nude mice carrying the HT-29BRAF mutant on V600E CRC subcutaneous xenograft tumors were treated with a single agent or combination of agents as shown in the oral legend. In both the single agent group and the triple combination group, compound a was used at 100mg/kg daily for the first two weeks of treatment and at 200mg/kg for the second two weeks of treatment. Values are mean ± SEM; sample size (n=5 mice/group). Tumor volumes are shown in the left panel. The percentage change in body weight from baseline is shown in the right panel.
Fig. 8: female nude mice carrying 5238-HX BRAF V600E CRC subcutaneous xenograft tumors (left panel: efficacy) or female nude mice carrying HT-29BRAF V600E CRC subcutaneous xenograft tumors (middle panel: efficacy, right panel: tolerance) were treated with a single agent or combination of agents shown in the oral legend (Dab: dabrafilinib; tran: trametinib (Trametinib)). Values are mean ± SEM; sample size: n=6-14 mice/group (5238-HX), n=6 rats/group (HT-29).
Fig. 9: female FVB mice bearing 24284-MA syngeneic subcutaneous tumors are treated with a single agent or combination of agents as shown in the oral legend. Values are mean ± SEM; sample size (n=5-6 mice/group).
Fig. 10: compound G YAP/TEAD inhibitor was used in combination with EGFR inhibitor EGF816 for lung cancer cell line PC9 with activating EGFR mutations.
Fig. 11: at the time of using YAP/TEAD inhibitor compound A or compound B and PI3K inhibitor NVP-QAU421 (or QAU 421) ((S) -N) 1 After 6 days of treatment with- (5- (2- (tert-butyl) pyrimidin-4-yl) -4-methylthiazol-2-yl) pyrrolidine-1, 2-dicarboxamide, the in vitro viability of the MCF7 breast cancer cell line (PIK 3CA mutant) was assessed using the celltiter glo assay. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 12: after 6 days of treatment with YAP/TEAD inhibitor compound D (2- ((2S, 4S) -5-chloro-2- ((((1 r, 4S) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide) in combination with various combinations of MAPK pathway inhibitors (MEK inhibitor MEKINIST/trimetinib/NVP-CFF 272 (CFF 272), BRAF/CRAF inhibitor NVP-LXH254 (LXH 254) and ERK inhibitor NVP-LTT462 (LTT 462)), the in vitro viability of the lung KRAS G12C mutant cell line LU-99 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 13: after 6 days of treatment with YAP/TEAD inhibitor compound E (2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((1 s,4 r) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide) in combination with various combinations of MAPK pathway inhibitors (BRAF inhibitor tafilar/darafinib/NVP-LIQ 288/LIQ288, MEK inhibitor MEKINIST/trimetinib/NVP-CFF 272/CFF272, BRAF/CRAF inhibitor NVP-LXH254 (LXH 254) and ERK inhibitor LTT462 (NVP-LTT 462)), the in vitro viability of the pulmonary BRAF mutant colorectal cell line SW-1417 was assessed using titerglo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 14: following 3 days of treatment with YAP/TEAD inhibitor compound D in combination with p53-HDM2 inhibitor NVP-HDM201 (HDM 201), CDKN2A deleted mesothelioma cell line MSTO-211H was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 15: after 3 days of treatment with YAP/TEAD inhibitor compound D in combination with CDK4/6 inhibitor NVP-LEE011 (LEE 011 or ribociclib), mesothelioma cell line MSTO-211H was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 16: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 17: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoprazole (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoprazole and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 18: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adagaramib (upper left), YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adagaramib and SHP2 inhibitor TNO155 (upper right) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adagaramib and SHP2 inhibitor RMC-4550 (lower), the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 19: after 7 days of treatment with YAP/TEAD inhibitor compound A in combination with SHP2 inhibitor TNO-155, the lung cancer cell line HCC44 was assessed for viability in vitro using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 20: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 21: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor sotoprazole (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor sotoprazole and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 22: lung cancer cell line HCC44 viability was assessed using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb (upper left), YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155 (upper right), and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550 (lower). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 23: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO-155, the lung cancer cell line HCC44 was assessed for viability in vitro using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 24: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 25: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor sotoprazole (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor sotoprazole and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 26: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550 (bottom), the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 27: colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 28: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib (upper) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib and SHP2 inhibitor TNO155 (lower), the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 29: colorectal cancer cell line SW1463 viability was assessed using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb (upper left), YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155 (upper right), and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550 (lower). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 30: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO-155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 31: colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 32: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor sotoracib (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor sotoracib and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 33: colorectal cancer cell line SW1463 viability was assessed using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb (upper left), YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155 (upper right), and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550 (lower). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 34: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO-155 (top), the in vitro viability of colorectal cancer cell line SW1463 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 35: colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom). Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 36: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor sotoracib (upper) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor sotoracib and SHP2 inhibitor TNO155 (lower), the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 37: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550 (bottom), the in vitro viability of colorectal cancer cell line SW1463 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 38: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 39: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 40: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 41: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 42: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 43: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 44: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 45: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 46: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 47: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 48: after 7 days of treatment with YAP/TEAD inhibitor compound A in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 49: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 50: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 51: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 52: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 53: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 54: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 55: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 56: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 57: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 58: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 59: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib (upper) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib and SHP2 inhibitor TNO155 (lower), the in vitro viability of lung cancer cell line LU65 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 60: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line LU65 was assessed using CellTiterGlo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 61: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443, the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 62: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443, the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 63: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 64: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 65: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 66: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 67: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 68: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 69: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 70: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 71: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 72: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 73: after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 74: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 (top) and YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155 (bottom), the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 75: after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Fig. 76: after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with CDK4/6 inhibitor NVP-LEE011 (LEE 011 or rebamacinib) (upper) and YAP/TEAD inhibitor compound a in combination with CDK4/6 inhibitor NVP-LEE011 (LEE 011 or rebamacinib) and KRAS G12C inhibitor JDQ443 (lower), the in vitro viability of lung cancer cell line NCI-H1792 was assessed using celltiter glo. Growth inhibition%: 0-99 = proliferation delay, 100 = growth arrest/arrest, 101-200 = reduction in cell number/cell death.
Detailed Description
As mentioned above, the object of the present invention is to find new combination therapies which selectively synergistically enhance the inhibition of proliferation and/or the induction of apoptosis.
Accordingly, the present invention provides the following numbered examples:
example 1. A method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a TEAD inhibitor in combination with a first additional therapeutically active agent and optionally a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
Example 2. A TEAD inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a first additional therapeutically active agent and optionally a second therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
Example 3. A combination comprising: i) TEAD inhibitors, ii) a first additional therapeutically active agent, and optionally iii) a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
Example 4. The method as described in example 1, the TEAD inhibitor as described in example 2, or the combination as described in example 3, wherein the first additional therapeutic agent is a KRAS G12/G13 inhibitor (e.g., a KRAS G12C inhibitor), e.g., when the second therapeutic agent is absent.
Example 5. The method of example 4, the TEAD inhibitor used as described in example 4, or the combination as described in example 4, wherein the second additional therapeutically active agent is present and is an SHP2 inhibitor.
Example 6. The TEAD inhibitor used as described in example 2, or the combination as described in example 3, according to the method described in example 1, wherein the first additional therapeutically active agent is an SHP2 inhibitor, e.g., when the second therapeutically active agent is not present.
Example 7. The method of example 1, the TEAD inhibitor used as described in example 2, or the combination of examples 3, wherein the first additional therapeutic agent is an EGFR inhibitor, e.g., when the second therapeutic agent is not present.
Example 8. The method as described in example 1, the TEAD inhibitor as described in example 2, or the combination as described in example 3, wherein the first additional therapeutically active agent is a PI3K inhibitor, e.g., when the second therapeutically active agent is not present.
Example 9. The method of example 1, the TEAD inhibitor used as described in example 2, or the combination of examples 3, wherein the first additional therapeutically active agent is an MDM2 inhibitor, e.g., when the second therapeutically active agent is not present.
Example 10. The TEAD inhibitor used as described in example 2, or the combination as described in example 3, according to the method described in example 1, wherein the first additional therapeutically active agent is a CDK4/6 inhibitor, e.g., when the second therapeutically active agent is not present.
Example 10a. The method of example 10, the TEAD inhibitor used as described in example 10, or the combination of examples 10, wherein the first additional therapeutically active agent is a CDK4/6 inhibitor (e.g., rebamactinib or a pharmaceutically acceptable salt thereof), and wherein the second therapeutically active agent is a KRAS G12C inhibitor (e.g., JDQ443 or a pharmaceutically acceptable salt thereof).
Example 10b the TEAD inhibitor as described in example 10a, used as described in example 10a, or the combination as described in example 10a, wherein the TEAD inhibitor is compound A (4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide) or a pharmaceutically acceptable salt.
Example 10c the TEAD inhibitor as described in example 10a, or the combination as described in example 10a, wherein the TEAD inhibitor is compound B (2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof.
Example 11. The method of example 1, the TEAD inhibitor used as described in example 2, or the combination as described in example 3, wherein the first additional therapeutic agent is a MEK inhibitor, e.g., when the second therapeutic agent is not present.
Example 12. The TEAD inhibitor used as described in example 2, or the combination as described in example 3, according to the method described in example 1, wherein the first additional therapeutically active agent is an ERK inhibitor, e.g., when the second therapeutically active agent is not present.
Example 13. The method of example 11 or example 12, the TEAD inhibitor used as described in example 11 or example 12, or the combination as described in example 11 or example 12, wherein a second additional therapeutically active agent is present, and wherein the second additional therapeutically active agent is a Raf inhibitor.
Example 14. The TEAD inhibitor used as described in example 2, or the combination as described in example 3, wherein the first additional therapeutically active agent is a cMET inhibitor, e.g., when the second therapeutically active agent is not present, as described in example 1.
Example 15. A cMET inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 16 a KRAS G12/G13 inhibitor (e.g., KRAS G12C inhibitor) for use in cancer treatment, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 17. The KRAS G12/G13 inhibitor for use as described in example 16, wherein the treatment further comprises administration of an SHP2 inhibitor.
Example 18. An SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 19. The SHP2 inhibitor for use as described in example 18, wherein the treatment further comprises administration of a KRAS G12/G13 inhibitor (e.g., a KRAS G12C inhibitor).
Example 20 a MEK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 21. An ERK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 22. A MEK inhibitor for use as described in example 20 or an ERK inhibitor for use as described in example 21, wherein the treatment further comprises administration of a Raf inhibitor.
Example 23. A Raf inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 24. The Raf inhibitor for use as described in example 23, wherein the treatment further comprises administration of a MEK inhibitor.
Example 25. The Raf inhibitor for use as described in example 23, wherein the treatment further comprises administration of an ERK inhibitor.
Example 26 an EGFR inhibitor for use in cancer treatment, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 27. A PI3K inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 28. An MDM2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
Example 29. A CDK4/6 inhibitor for use in the treatment of cancer, wherein said treatment further comprises administering a TEAD inhibitor.
Example 30 the method according to any one of examples 1 and 4 to 14, the TEAD inhibitor according to any one of examples 2 and 4 to 14, the combination according to any one of examples 3 to 14, the cMET inhibitor according to example 15, the KRAS G12/G13 inhibitor according to example 16 or example 17, the SHP2 inhibitor according to example 18 or example 19, the MEK inhibitor according to example 20 or example 22, the Raf inhibitor according to any one of examples 23 to 25, the EGFR inhibitor according to example 26, the PI3K inhibitor according to example 27, the MDM2 inhibitor according to example 28, or the 4/6 inhibitor according to example 29, wherein the CDK inhibitor is a YAP/TAZ-protein-TEAD interaction inhibitor.
Example 31 the method of example 30, the TEAD inhibitor of example 30, the combination of example 30, the cMET inhibitor of example 30, the KRAS G12/G13 inhibitor of example 30, the SHP2 inhibitor of example 30, the ERK inhibitor of example 30, the Raf inhibitor of example 30, the EGFR inhibitor of example 30, the PI3K inhibitor of example 30, the MDM2 inhibitor of example 30, or the CDK4/6 inhibitor of example 30, wherein the TEAD inhibitor is a TEAD inhibitor of formula (I), or a pharmaceutically acceptable salt thereof, e.g., compound A (4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-3-dihydro-3-benzofuran-6-hydroxy-5-methylbenzof2) -2-ethoxy-5-methylbenzofa pharmaceutically acceptable salt thereof, or compound B (2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof.
Example 31a. The TEAD inhibitor as described in example 31, the combination of the TEAD inhibitor as described in example 31, the cMET inhibitor as described in example 31, the KRAS G12/G13 inhibitor as described in example 31, the SHP2 inhibitor as described in example 31, the MEK inhibitor as described in example 31, the Raf inhibitor as described in example 31, the EGFR inhibitor as described in example 31, the PI3K inhibitor as described in example 31, the MDM2 inhibitor as described in example 31, or the CDK4/6 inhibitor as described in example 31, wherein the D inhibitor is the pharmaceutically acceptable salt of compound A (4- ((2S, 4S) -5-chloro-6-fluoro-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydro-benzofuran-4-yl) -5-fluoro-2- (hydroxyethoxy) -2-methyl-6) nicotinamide.
Example 31B. TEAD inhibitors as described in example 31, cMET inhibitors as described in example 31, KRAS G12/G13 inhibitors as described in example 31, SHP2 inhibitors as described in example 31, ERK inhibitors as described in example 31, raf inhibitors as described in example 31, EGFR inhibitors as described in example 31, PI3K inhibitors as described in example 31, MDM2 inhibitors as described in example 31, or CDK4/6 inhibitors as described in example 31, wherein the D inhibitor is the compound B (2- ((2S, 3S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydro-benzofuran-4-yl) -3-fluoro-benzamide) or a pharmaceutically acceptable salt thereof.
Example 31c TEAD inhibitors as described in example 31, combinations of TEAD inhibitors as described in example 31, cMET inhibitors as described in example 31, KRAS G12/G13 inhibitors as described in example 31, SHP2 inhibitors as described in example 31, MEK inhibitors as described in example 31, ERK inhibitors as described in example 31, raf inhibitors as described in example 31, EGFR inhibitors as described in example 31, PI3K inhibitors as described in example 31, MDM2 inhibitors as described in example 31, or CDK4/6 inhibitors as described in example 31, wherein the D inhibitor isOr a pharmaceutically acceptable salt thereof.
The method of any one of examples 1, 4, 5, 30 and 31, the TEAD inhibitor of any one of examples 2, 4, 5, 30 and 31, the combination of any one of examples 3 to 5, 30 and 31, the KRAS G12/G13 inhibitor of any one of examples 16, 17, 30 and 31, or the SHP2 inhibitor of any one of examples 19, 30 and 31, wherein the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor selected from the group consisting of: compound C, sotoracicb (amagen), adaglazeb (Mirati corporation), D-1553 (benefit organism (innoki)), BI1701963 (Boehringer)), GDC6036 (Roche), JNJ74699157 (johner company (J & J)), X-Chem KRAS (X-Chem corporation), LY3537982 (gilly), BI1823911 (bolinger corporation), AS KRAS G12C (sub-bulk pharmaceutical corporation (Ascentage Pharma)), SF KRAS G12C (Sanofi)), RMC032 (revolution pharmaceutical corporation (Revolution Medicine)), JAB-21822 (ganofi pharmaceutical corporation (Jacobio Pharmaceuticals)), AST-KRAS G12C (Ai Lisi pharmaceutical corporation (Allist Pharmaceuticals)), AZ KRAS G12C (aszeneca) and trau 12C (New York University)), and pharmaceutically acceptable salts thereof (Revolution Medicines).
Example 32a the method of example 32, the TEAD inhibitor of example 32, the combination of example 32, the KRAS G12/G13 inhibitor of example 32, or the SHP2 inhibitor of example 32, wherein the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor selected from the group consisting of: compound C, sotoracicb (mecianin) (also known as AMG 510) and adaglazeb (Mirati), or a pharmaceutically acceptable salt thereof.
Example 33 the method of example 32, the TEAD inhibitor of example 32, the combination of example 32, the KRAS G12/G13 inhibitor of example 32, or the SHP2 inhibitor of example 32, wherein the KRAS G12/G13 inhibitor is KRAS G12C inhibitor compound C (1- {6- [ (4M) -4- (5-chloro-6-methyl-1H-indazol-4-yl) -5-methyl-3- (1-methyl-1H-indazol-5-yl) -1H-pyrazol-1-yl ] -2-azaspiro [3.3] heptan-2-yl } prop-2-en-1-one) or sottorx (AMG 510), or a pharmaceutically acceptable salt thereof.
Example 34 TEAD inhibitors as described in example 33, combinations as described in example 33, KRAS G12/G13 inhibitors as described in example 33, or SHP2 inhibitors as described in example 33, wherein the KRAS G12/G13 inhibitor is KRAS G12C inhibitor compound C, or a pharmaceutically acceptable salt thereof.
Example 34a. The TEAD inhibitor as described in example 33, the combination as described in example 33, the KRAS G12/G13 inhibitor as described in example 33, or the SHP2 inhibitor as described in example 33, wherein the KRAS G12/G13 inhibitor is sotoracib (AMG 510), or a pharmaceutically acceptable salt thereof.
Example 34b. The method of example 32, the TEAD inhibitor of example 32, the combination of examples 32, the KRAS G12/G13 inhibitor of example 32, or the SHP2 inhibitor of example 32, wherein the KRAS G12/G13 inhibitor is adaglazecloth, or a pharmaceutically acceptable salt thereof.
The method of any one of examples 1, 5, 6 and 30 to 34, the TEAD inhibitor used in any one of examples 2, 5, 6 and 30 to 34, the combination of any one of examples 3, 5, 6 and 30 to 34, the KRAS G12/G13 inhibitor used in any one of examples 17 and 30 to 34, or the SHP2 inhibitor used in any one of examples 18, 19 and 30 to 34, wherein the SHP2 inhibitor is selected from the group consisting of: TNO155 (North Co., ltd.), JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche Co.), SAR442720 (Sainofil Co.), RMC4550 (Innovative pharmaceutical Co.), RMC4630 (Ind. Pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qinghai medical science Co., ltd.), SH3809 (Nanjing Sanhome), PF0724982 (Congo Co.), ERAS601 (Erasca Co.), RX-SHP2 (Redx pharmaceutical Co., redx Pharma), ICP189 (Innocare), HBI2376 (Hu Asian (HUYA Bioscience), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Datsukhiya Biopharmaceutical Co., ltd.), and Tatsuka & O37-37 or pharmaceutical salts thereof are acceptable.
Example 35a. The method of example 35, the TEAD inhibitor as described in example 35, the combination of the KRAS G12/G13 inhibitor as described in example 35, or the SHP2 inhibitor as described in example 35, wherein the SHP2 inhibitor is selected from the group consisting of: TNO155, RMC4550 and RMC4630, or pharmaceutically acceptable salts thereof.
Example 36. TEAD inhibitors as described in example 35, combinations of TEAD inhibitors as described in example 35, KRAS G12/G13 inhibitors as described in example 35, or SHP2 inhibitors as described in example 35, wherein the SHP2 inhibitor is TNO155, or a pharmaceutically acceptable salt thereof.
Example 36a. The TEAD inhibitor as described in example 35, the combination of the TEAD inhibitors as described in example 35, the KRAS G12/G13 inhibitor as described in example 35, or the SHP2 inhibitor as described in example 35, wherein the SHP2 inhibitor is RMC4550 or RMC4630, or a pharmaceutically acceptable salt thereof.
Embodiment 37 the method of any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use of any one of embodiments 2, 4, 30 and 31, the combination of any one of embodiments 3, 4, 30 and 31, or the cMET inhibitor for use of embodiment 15, wherein the cMET inhibitor is selected from the group consisting of: crizotinib (crizotinib), carbamazetinib (capmatiib), terpontinib (tepontinib), AMG337, cabozantinib (cabozantinib), cerclatinib (savoniinib) (AZD 6094, HMPL-504), tivantinib (tivantinib), furitinib (foretinib), wo Liti, von ilinib, SU11274, PHA 665752, SGX523, BAY-853474, KRC-408, T-1840383, MK-2461, BMS-777607, JNJ-38877605, tivantinib (ARQ 197), PF-0421703, MGCD265 BMS-754807, BMS-794833, AMG-458, NVP-BVU972, AMG-208, govastatin (golvantinib), norcantharidin, S49076, SAR125844, mersatinib (merestinib) (LY 2801653), onatuzumab (onartuzumab), ematuzumab (emibetuzumab), SAIT301, ABT-700, DN30, LY3164530, rituximab (rilotumumab), non-lattuzumab (ficlatuzumab), TAK701 and YYYB-101, or pharmaceutically acceptable salts thereof.
Example 38. The TEAD inhibitor used as described in example 37, the combination as described in example 37, or the cMET inhibitor used as described in example 37, wherein the cMET inhibitor is: i) Terpontinib, or ii) carbamazepine, or a pharmaceutically acceptable salt thereof.
Embodiment 39 the method of any one of embodiments 1, 14, 30, and 31, the TEAD inhibitor used as described in any one of embodiments 2, 4, 30, and 31, the combination as described in any one of embodiments 3, 4, 30, and 31, or the EGFR inhibitor used as described in embodiment 26, wherein the EGFR inhibitor is selected from the group consisting of: cetuximab (cetuximab), panitumumab (panitumumab), erlotinib (erlotinib), gefitinib (gefitinib), oxcetinib (osiertinib), and nazatinib (nazartiinib), or a pharmaceutically acceptable salt thereof.
Example 40. The method of example 39, the TEAD inhibitor as described in example 39, the combination of example 39, or the EGFR inhibitor as described in example 39, wherein the EGFR inhibitor is nazatinib (also referred to as EGF 816) or a pharmaceutically acceptable salt thereof.
Example 41 the method of any one of examples 1, 14, 30 and 31, the TEAD inhibitor for use of any one of examples 2, 4, 30 and 31, the combination of any one of examples 3, 4, 30 and 31, or the PI3K inhibitor for use of example 27, wherein the PI3K inhibitor is selected from the group consisting of: AMG511, bupiriib (buparlisib), idelalisib (Idelalisib), copanlisib (Copanlisib), du Weili sibirib (Duvelisib), aperilisib (alpeliib), QAU421 and erbilib (ubralib), or pharmaceutically acceptable salts thereof.
Embodiment 42. The method of any one of embodiments 1, 14, 30, and 31, the TEAD inhibitor for use of any one of embodiments 2, 4, 30, and 31, the combination of any one of embodiments 3, 4, 30, and 31, or the MDM2 inhibitor for use of embodiment 28, wherein the MDM2 inhibitor is selected from the group consisting of: nutlin-3a, idanean (idaranulin) (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytans (milademan) and HDM201 (also known as sireidrelin), or pharmaceutically acceptable salts thereof.
Example 43 the method of example 42 using the TEAD inhibitor of example 42, the combination of example 42, or the MDM2 inhibitor of example 42, wherein the MDM2 inhibitor is HDM201 or a pharmaceutically acceptable salt thereof.
Example 44 the method of any one of examples 1, 14, 30 and 31, the TEAD inhibitor for use of any one of examples 2, 4, 30 and 31, the combination of any one of examples 3, 4, 30 and 31, or the CDK4/6 inhibitor for use of example 29, wherein the CDK4/6 inhibitor is selected from the group consisting of: rebaudinib, palbociclib (palbociclib) and abberacilib (abemaciclib) or pharmaceutically acceptable salts thereof.
Example 45. The method of example 44, the TEAD inhibitor as described in example 44, the combination as described in example 44, or the CDK4/6 inhibitor as described in example 44, wherein the CDK4/6 inhibitor is rebamactinib or a pharmaceutically acceptable salt thereof.
Embodiment 46 the method of any one of embodiments 1, 14, 30, and 31, the TEAD inhibitor used as described in any one of embodiments 2, 4, 30, and 31, the combination as described in any one of embodiments 3, 4, 30, and 31, or the MEK inhibitor used as described in embodiment 20 or embodiment 22, or the Raf inhibitor used as described in embodiment 24, wherein the MEK inhibitor is selected from the group consisting of: pimasitinib (pimasetinib), PD-0325901, semantenib, trametinib, bemetinib (binimetinib) and cobitinib (cobimetinib), or pharmaceutically acceptable salts thereof.
Example 47 the method of example 46 uses a TEAD inhibitor as described in example 46, a combination of the methods of example 46 uses a MEK inhibitor as described in example 46, or uses a Raf inhibitor as described in example 46, wherein the MEK inhibitor is trametinib or a pharmaceutically acceptable salt thereof.
Embodiment 48 the method of any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor of any one of embodiments 2, 4, 30 and 31, the combination of any one of embodiments 3, 4, 30 and 31, or the ERK inhibitor of embodiment 21 or embodiment 22, or the Raf inhibitor of embodiment 25, wherein the ERK inhibitor is selected from the group consisting of: ulitinib (ulixertiinib), GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523, or pharmaceutically acceptable salts thereof.
Example 49 the TEAD inhibitor as described in example 48, the combination as described in example 48, the ERK inhibitor as described in example 48, or the Raf inhibitor as described in example 48, wherein the ERK inhibitor is LTT462 (rineterkib)) or ulitinib, or a pharmaceutically acceptable salt thereof.
The method of any one of examples 1, 14, 30, 31 and 46 to 49, the TEAD inhibitor of any one of examples 2, 4, 30, 31 and 46 to 49, the combination of any one of examples 3, 4, 30, 31 and 46 to 49, the MEK inhibitor of example 22, the ERK inhibitor of example 22, or the Raf inhibitor of any one of examples 23 to 25, wherein the Raf inhibitor is selected from the group consisting of: bei Fafei Ni (belvarafanib), naprafeanib (also known as LXH 254), encofenib, vitamin Mo Feini (vemurafenib) and Darafanib, or pharmaceutically acceptable salts thereof.
Example 51. The method of example 50, the TEAD inhibitor of example 50, the combination of example 50, the MEK inhibitor of example 50, the ERK inhibitor of example 50, or the Raf inhibitor of example 50, wherein the Raf inhibitor is dabrafenib or LXH254 (naprafenib), or a pharmaceutically acceptable salt thereof.
The method of any one of examples 1, 4 to 14 and 30 to 51 using the TEAD inhibitor of any one of examples 2, 4 to 14 and 30 to 51 using the cMET inhibitor of any one of examples 15, 30, 31, 37 and 38 using the KRAS G12/G13 inhibitor of any one of examples 16, 17 and 30 to 36 using the EGFR inhibitor of any one of examples 18, 19 and 30 to 36 using the fap 2 inhibitor of any one of examples 20, 22, 30, 31, 46, 47, 50 and 51 using the ERK inhibitor of any one of examples 21, 22, 30, 31 and 48 to 51 using the Raf inhibitor of any one of examples 23 to 25, 30, 31 and 46 to 51 using the EGFR inhibitor of any one of examples 26, 30, 31, 39 and 40 using the EGFR inhibitor of any one of examples 27, 31, 39 and 40 using the mdk inhibitor of any one of examples 30, 31 and 30, and 45 using the example 4 using the me inhibitor of any one of examples 30, 31 and 45 using the tea inhibitor of any one of examples 4, 30 and 30 to 51 using the example 4, 30, 31 and 30 and 48 to 51 using the example 4.
The method of any one of examples 1, 4 to 14 and 30 to 52, the TEAD inhibitor of any one of examples 2, 4 to 14 and 30 to 52, the cMET inhibitor of any one of examples 15, 30, 31, 37, 38 and 52, the KRAS G12/G13 inhibitor of any one of examples 16, 17, 30 to 36 and 52, the SHP2 inhibitor of any one of examples 18, 19, 30 to 36 and 52, the MEK inhibitor of any one of examples 20, 22, 30, 31, 46, 47 and 50 to 52, the ERK inhibitor used in any one of examples 21, 22, 30, 31 and 48 to 52, the Raf inhibitor used in any one of examples 23 to 25, 30, 31 and 46 to 52, the EGFR inhibitor used in any one of examples 26, 30, 31, 39, 40 and 52, the PI3K inhibitor used in any one of examples 27, 30, 31, 41 and 52, the MDM2 inhibitor used in any one of examples 28, 30, 31, 42, 43 and 52, or the CDK4/6 inhibitor used in any one of examples 29 to 31, 44, 45 and 52, wherein the cancer is selected from the group consisting of: breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma (medulloblastoma), head and neck cancer, sarcoma, squamous cell carcinoma, epithelioid vascular endothelial tumor, ependymal tumor, and bone cancer, for example, wherein the cancer is malignant pleural mesothelioma.
Example 53a. TEAD inhibitors as described in example 53, cMET inhibitors as described in example 53, KRAS G12/G13 inhibitors as described in example 53, SHP2 inhibitors as described in example 53, ERK inhibitors as described in example 53, raf inhibitors as described in example 53, EGFR inhibitors as described in example 53, PI3K inhibitors as described in example 53, MDM2 inhibitors as described in example 53, or CDK4/6 inhibitors as described in example 53, wherein the cancer is colorectal cancer or lung cancer.
The method of any one of examples 1, 4 to 14 and 30 to 53a, the TEAD inhibitor of any one of examples 2, 4 to 14 and 30 to 53a, the cMET inhibitor of any one of examples 15, 30, 31, 37, 38 and 53a, the KRAS G12/G13 inhibitor of any one of examples 16, 17, 30 to 36 and 53a, the SHP2 inhibitor of any one of examples 18, 19, 30 to 36 and 53a, the MEK inhibitor of any one of examples 20, 22, 30, 31, 46, 47 and 50 to 53a, the ERK inhibitor for use according to any one of examples 21, 22, 30, 31 and 48 to 53a, the Raf inhibitor for use according to any one of examples 23 to 25, 30, 31 and 46 to 53a, the EGFR inhibitor for use according to any one of examples 26, 30, 31, 39, 40 and 53a, the PI3K inhibitor for use according to any one of examples 27, 30, 31, 41 and 53a, the MDM2 inhibitor for use according to any one of examples 28, 30, 31, 42, 43 and 53a, or the CDK4/6 inhibitor for use according to any one of examples 29 to 31, 44, 45 and 53a, wherein the cancer is a KRAS G12C mutant cancer.
The method of any one of examples 1, 4 to 14 and 30 to 53, the TEAD inhibitor of any one of examples 2, 4 to 14 and 30 to 53, the cMET inhibitor of any one of examples 15, 30, 31, 37, 38, 52 and 53, the KRAS G12/G13 inhibitor of any one of examples 16, 17, 30 to 36, 52 and 53, the SHP2 inhibitor of any one of examples 18, 19, 30 to 36, 52 and 53, the MEK inhibitor of any one of examples 20, 22, 30, 31, 46, 47 and 50 to 53, the ERK inhibitor of any one of examples 21, 22, 30, 31 and 48 to 53, the Raf inhibitor for use according to any one of claims 23 to 25, 30, 31 and 46 to 53, the EGFR inhibitor for use according to any one of claims 26, 30, 31, 39, 40, 52 and 53, the PI3K inhibitor for use according to any one of claims 27, 30, 31, 41, 52 and 53, the MDM2 inhibitor for use according to any one of claims 28, 30, 31, 42, 43, 52 and 53, or the CDK4/6 inhibitor for use according to any one of claims 29 to 31, 44, 45, 52 and 53, wherein the tea d inhibitor is administered on each of the first 3 days of a 7 day treatment cycle, and wherein the treatment consists of at least two treatment cycles.
Example 55. TEAD inhibitor as described in example 54, cMET inhibitor as described in example 54, KRAS G12/G13 inhibitor as described in example 54, SHP2 inhibitor as described in example 54, MEK inhibitor as described in example 54, ERK inhibitor as described in example 54, raf inhibitor as described in example 54, EGFR inhibitor as described in example 54, PI3K inhibitor as described in example 54, MDM2 inhibitor as described in example 54, or CDK4/6 inhibitor as described in example 54, wherein the daily dose of TEAD inhibitor is 15mg to 100mg per day of administration.
Example 56A TEAD inhibitor as described in example 55, a cMET inhibitor as described in example 55, a KRAS G12/G13 inhibitor as described in example 55, a SHP2 inhibitor as described in example 54, a MEK inhibitor as described in example 55, an ERK inhibitor as described in example 55, a Raf inhibitor as described in example 55, an EGFR inhibitor as described in example 55, a PI3K inhibitor as described in example 55, a MDM2 inhibitor as described in example 55, or a CDK4/6 inhibitor as described in example 55, wherein the daily dose of the TEAD inhibitor is 15mg, 30mg, 45mg, 60mg, 75mg, 90mg or 100mg per day of administration.
It has been determined that the combinations of the invention are useful for the effective treatment of cancer, for example, due to synergistic effects in inhibiting cell proliferation and/or inducing apoptosis.
In embodiments of any of the aspects of the invention, the TEAD inhibitor is a YAP/TAZ-TEAD protein-protein interaction inhibitor.
In embodiments of any of the various aspects of the invention, the TEAD inhibitor is a TEAD inhibitor of formula (I), or a pharmaceutically acceptable salt thereof, such as compound A (4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or compound B (2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof,
wherein the method comprises the steps of
W is selected from O, and CH-R w ；
X is selected from CH, and N;
y is selected from CH, and N;
z is selected from CH 2 O, and NH;
wherein when Y is N, W is CH-R w And Z is O;
a is selected from
(i) Phenyl optionally substituted with: halogenating; or halogenated C 1 -C 3 An alkoxy group;
(ii) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, the aromatic heterocycle being optionally substituted by: a hydroxyl group; c (C) 1 -C 3 An alkoxy group; or oxo; and
(iii) A halogenated benzodioxole moiety having the formula:
R w selected from: (i) hydrogen; (ii) hydroxy; (iii) C (C) 1 -C 3 An alkoxy group; (iv) hydroxy-C 1 -C 3 An alkyl group; (v) C (C) 1 -C 3 An alkyl group; and (vi) C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group;
q is selected from: (i) -C (R) 7 ) 2 -N(R 8 )-R 1 The method comprises the steps of carrying out a first treatment on the surface of the (ii) A 9-or 10-membered partially saturated heteroaryl group containing at least one N heteroatom; and (iii) comprises a compound selected from N, O, S, -S (=o), and-S (=o) 2 A 4-, 5-, or 6-membered saturated heterocyclic ring of at least one heteroatom or heteroatom group, provided that at least one N heteroatom is present, wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from the group consisting of: hydroxy, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo and C 1 -C 3 Alkylene groups, which form a bridge between two ring atoms of a saturated heterocyclic ring, thereby forming a bridged bicyclic structure;
R 1 selected from: (i) hydrogen; (ii) C (C) 1 -C 6 Alkyl, optionally deuterated; and (iii) (CH 2 ) 0-2 R 1a ；
R 1a Selected from: (i) Hydroxy C 1 -C 4 An alkyl group; (ii) C (C) 1 -C 3 An alkoxy group; (iii) A 5-or 6-membered saturated heterocyclic ring comprising at least one heteroatom selected from N and O, the saturated heterocyclic ring optionally being independently substituted one or more times by: c (C) 1 -C 3 An alkyl group; (CH) 2 ) 0-1 C (O) di (C) 1 -C 3 Alkyl) amino; SO (SO) 2 C 1 -C 3 An alkyl group; c (O) C 1 -C 3 An alkyl group; or oxo; (iv) C (C) 3 -C 6 Cycloalkyl optionally substituted one or more times independently with: a hydroxyl group; hydroxy C 1 -C 4 An alkyl group; c (C) 1 -C 6 An alkoxy group; c (O) OC 1 -C 3 An alkyl group; c (C)O 2 H；SO 2 C 1 -C 3 An alkyl group; halogenated C 1 -C 3 An alkyl group; NHR (NHR) 1b ；(CH 2 ) 0-1 C(O)NR 1c R 1d ；C 1 -C 6 An alkyl group; halogenated C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group; halogenating; a 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; or two R 1e The group(s) is (are) a radical,
wherein two R's attached to the same carbon atom 1e Together with the carbon atom to which they are attached, form a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or C 3 -C 6 Cycloalkyl, the saturated heterocycle or cycloalkyl being optionally substituted with: hydroxy or oxo;
R 1b selected from: (i) C (O) C 1 -C 3 An alkyl group; and (ii) SO 2 C 1 -C 3 An alkyl group;
R 1c and R is 1d Each independently selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; and (iii) hydroxy C 1 -C 4 An alkyl group;
R 2 selected from: (i) hydrogen; and (ii) halo;
R 3 selected from: (i) halo; (ii) Halogenated C 1 -C 3 An alkyl group; and (iii) cyano;
R 4 selected from: (i) hydrogen; (ii) halo; and (iii) C 1 -C 3 An alkyl group;
R 5 selected from: (i) hydrogen; (ii) C (C) 1 -C 6 Alkoxy optionally substituted with: c (C) 3 -C 6 Cycloalkyl; CO 2 H；SO 2 C 1 -C 3 An alkyl group; a 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; or a 5-or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally being C (O) C 1 -C 3 Alkyl substitution;
(iii) Halogenating; (iv) Hydroxy C 1 -C 6 An alkoxy group, wherein the alkoxy group is optionally deuterated; (v) Optionally taken up by hydroxy groupsSubstituted halogenated C 1 -C 6 An alkoxy group; (vi) S-halo C optionally substituted with hydroxy 1 -C 3 An alkyl group; (vii) C (C) 1 -C 3 Alkoxy C 1 -C 3 An alkoxy group; (viii) NR (NR) 5a R 5b ；(ix)C 1 -C 3 An alkyl group; (x) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; and (xi) hydroxy;
R 5a and R is 5b Each independently selected from: (i) hydrogen; and (ii) C 1 -C 3 An alkyl group;
or alternatively
R 5a And R is 5b Together with the nitrogen atom to which they are attached, form a 5-or 6-membered saturated heterocyclic ring, which optionally additionally carries a hydroxyl group;
R 6 selected from: (i) hydrogen; (ii) cyano; (iii) C (O) NHR 6a ；(iv)NHR 6b The method comprises the steps of carrying out a first treatment on the surface of the And (v) NH 2 Or hydroxy-substituted C 1 -C 3 An alkoxy group;
R 6a selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; (iii) C (C) 3 -C 6 Cycloalkyl; (iv) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, the aromatic heterocycle being optionally substituted by: c (C) 1 -C 3 An alkyl group;
R 6b is covered by NH 2 Or hydroxy-substituted C 1 -C 3 An alkyl group;
R 7 each independently selected from hydrogen and C 1 -C 3 An alkyl group; and is also provided with
R 8 Is hydrogen or C 1 -C 3 -an alkyl group.
In embodiments of any of the aspects of the invention, when the KRAS G12/G13 inhibitor is present, the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor.
In embodiments of any of the aspects of the invention, when a KRAS G12/G13 inhibitor is present, the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor selected from the group consisting of: compound C, sotoracicb (mecianin), adaglazeb (Mirati), D-1553 (benefit organism), BI1701963 (bringer), GDC6036 (roc), JNJ74699157 (prednisone), X-Chem KRAS (X-Chem), LY3537982 (gili), BI1823911 (bringer), AS KRAS G12C (flourishing pharmaceutical company), SF KRAS G12C (cerofil company), RMC032 (revolutionary pharmaceutical company), JAB-21822 (additive pharmaceutical company), AST-KRAS G12C (Ai Lisi pharmaceutical company), AZ KRAS G12C (aslicang company), NYU-12VC1 (new york university) and RMC6291 (revolutionary pharmaceutical company), or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, when the KRAS G12/G13 inhibitor is present, the KRAS G12/G13 inhibitor is KRAS G12C inhibitor compound C (1- {6- [ (4M) -4- (5-chloro-6-methyl-1H-indazol-4-yl) -5-methyl-3- (1-methyl-1H-indazol-5-yl) -1H-pyrazol-1-yl ] -2-azaspiro [3.3] heptan-2-yl } prop-2-en-1-one) or AMG510, or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when the KRAS G12/G13 inhibitor is present, the KRAS G12/G13 inhibitor is KRAS G12C inhibitor compound C or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when an SHP2 inhibitor is present, the SHP2 inhibitor is selected from the group consisting of: TNO155 (North Co., ltd.), JAB3068 (Gasci Co., ltd.), JAB3312 (Gasci Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sainofil Co., ltd.), RMC4550 (Innovative Co., ltd.), RMC4630 (Innovative Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai green and Moss medical science Co., ltd.), SH3809 (Nanj holy and Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP189 (Nocheng, santa Clara Co., ltd.), HBI2376 (Shanghai Co., ltd.), ETS001 (Shanghai biological pharmaceutical Co., ltd.), TAS-ASTX (Datsukamura pharmaceutical Co., ltd.) and X-37-SHP2 (X-37), or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, the SHP2 inhibitor, when present, is TNO155 or a pharmaceutically acceptable salt thereof.
In the alternativeIn embodiments, the SHP2 inhibitor, when present, is RMC-4550 or a pharmaceutically acceptable salt thereof, i.e(RMC-4550)。
In alternative embodiments, the SHP2 inhibitor, when present, is RMC-4630 or a pharmaceutically acceptable salt thereof, i.e(RMC-4630)。
In an embodiment of any one of the aspects of the invention, when a cMET inhibitor is present, the cMET inhibitor is selected from the group consisting of: crizotinib, carbamazetinib, terpontinib, AMG337, cabotinib, certetinib (AZD 6094, HMPL-504), tivantinib, furitinib, wo Liti, SU11274, PHA 665752, SGX523, BAY-853474, KRC-408, T-1840383, MK-2461, BMS-777607, JNJ-38877605, tivantinib (ARQ 197), PF-04217403, MGCD265, BMS-754807, BMS-794833, AMG-458, NVP-BVU972, AMG-208, govatinib, norcantharidin, S49076, SAR125844, mexitinib (2801653), onabantuzumab, imatuzumab, SAIT301, ABT-700, DN30, LY3164530, rituximab, TAK and yybb-101, or pharmaceutically acceptable salts thereof.
In an embodiment of any of the aspects of the invention, when a cMET inhibitor is present, the cMET inhibitor is: i) Terpontinib, or ii) carbamazepine, or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when an EGFR inhibitor is present, the EGFR inhibitor is selected from the group consisting of: cetuximab, panitumumab, erlotinib, gefitinib, oxtinib and nazatinib, or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, the EGFR inhibitor, when present, is nazatinib (also known as EGF 816) or a pharmaceutically acceptable salt thereof.
In an embodiment of any one of the aspects of the invention, when a PI3K inhibitor is present, the PI3K inhibitor is selected from the group consisting of: AMG511, bupanii, erila, copani, du Weili sibutra, apirism, QAU421 and erbitux, or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when an MDM2 inhibitor is present, the MDM2 inhibitor is selected from the group consisting of: nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine and HDM201 (also known as sirodelin), or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, when an MDM2 inhibitor is present, the MDM2 inhibitor is HDM201 or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when a CDK4/6 inhibitor is present, the CDK4/6 inhibitor is selected from the group consisting of: rebaudiana, palbociclib, and abbe west, or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, the CDK4/6 inhibitor, when present, is rebaudiana or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when a MEK inhibitor is present, the MEK inhibitor is selected from the group consisting of: pimosaic, PD-0325901, semantenib, tramatinib, bemetinib and cobratinib, or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, the MEK inhibitor, when present, is trametetinib or a pharmaceutically acceptable salt thereof.
In embodiments of any of the aspects of the invention, when an ERK inhibitor is present, the ERK inhibitor is selected from the group consisting of: ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523, or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, the ERK inhibitor, when present, is LTT462 (rilnetbase cloth) or ulitinib, or a pharmaceutically acceptable salt thereof.
In an embodiment of any one of the aspects of the invention, when present, the Raf inhibitor is selected from the group consisting of: bei Fafei, naprafenib (also known as LXH 254), encofenib, vitamin Mo Feini and Darafenib, or pharmaceutically acceptable salts thereof.
In embodiments of any of the aspects of the invention, the Raf inhibitor, when present, is dabrafenib or LXH254 (naprafenib), or a pharmaceutically acceptable salt thereof.
In embodiments, the cancer is a TEAD-dependent cancer.
In embodiments, the cancer is selected from the group consisting of: breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma, head and neck cancer, sarcoma, squamous cell carcinoma, epithelioid vascular endothelial tumor, ependymal tumor and bone cancer.
In embodiments, the TEAD inhibitor is administered each of the first 3 days of a 7 day treatment cycle, and wherein the treatment consists of at least two treatment cycles. In an embodiment, the daily dose of TEAD inhibitor per administration day is 15mg to 100mg. In embodiments, the daily dose of TEAD inhibitor per administration day is 15mg, 30mg, 45mg, 60mg, 75mg, 90mg or 100mg.
Definition of the definition
The terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. When plural is used for a compound, patient, cancer, etc., this also means the singular of the compound, patient, etc.
Reference in the specification to "the invention" is intended to reflect embodiments of the invention disclosed in the specification and should not be taken as unnecessarily limiting the claimed subject matter.
As used herein, the term "synergistic effect" refers to the effect of two or three therapeutic agents that produce an effect, e.g., slowing the progression of a proliferative disease (particularly cancer or a symptom thereof), that is greater than the simple addition of the effects of each drug administered by itself. The synergistic effect can be calculated, for example, using suitable methods such as Sigmoid-Emax equations (Holford, n.h.g. and Scheiner, L.B., clin.Pharmacokinet [ clinical pharmacokinetics ]6:429-453 (1981)), loewe additivity equations (Loewe, s. And Muischnek, h.), arch.exp.pathel Pharmacol. Experimental pathology and pharmacology archives ]114:313-326 (1926)), and median equations (Chou, t.c. and Talalay, p., adv.enzyme regulation progress [ enzyme regulation study ]22:27-55 (1984)). Each of the equations mentioned above may be applied to experimental data to generate corresponding charts to aid in assessing the effect of the drug combination. The corresponding graphs associated with the above-mentioned equations are the concentration-effect curve, the isobologram curve and the combination index curve, respectively.
The term "pharmaceutically acceptable salt" refers to salts that retain the biological effectiveness and properties of the compound and are typically not biologically or otherwise undesirable. Due to the presence of amino groups, the compounds may be capable of forming acid addition salts.
Unless otherwise indicated or explicitly indicated herein, references to therapeutic agents useful in the pharmaceutical combinations of the present invention include the free base of the compound and all pharmaceutically acceptable salts of the compound.
The term "combination" or "pharmaceutical combination" is defined herein to mean a fixed combination in the form of one dosage unit, a non-fixed combination for combined administration or a kit of parts, wherein the therapeutic agents may be administered together simultaneously, independently or separately over a time interval, which preferably allows the combination partners to exhibit a synergistic, e.g. synergistic effect. Thus, individual compounds of the pharmaceutical combinations of the invention may be administered simultaneously or sequentially.
Furthermore, the pharmaceutical combination of the invention may be in the form of a fixed combination, or in the form of a non-fixed combination.
The term "fixed combination" means that the therapeutic agents (e.g., the individual compounds in the combination) are in the form of a single entity or dosage form.
The term "non-fixed combination" means that the therapeutic agents (e.g., the individual compounds in the combination) are administered to the patient either simultaneously or sequentially as separate entities or dosage forms, without specific time limitations, wherein preferably such administration provides therapeutically effective levels of both therapeutic agents in the body of a subject, e.g., a mammal or human in need thereof.
The pharmaceutical combination may further comprise at least one pharmaceutically acceptable carrier. Accordingly, the present invention relates to a pharmaceutical composition comprising a pharmaceutical combination according to the invention and at least one pharmaceutically acceptable carrier.
As used herein, the term "carrier" or "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, pharmaceutical stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavoring agents, dyes, and the like, and combinations thereof, as would be understood by one of skill in the art (see, e.g., remington's Pharmaceutical Sciences [ leington's pharmaceutical science ], 18 th edition, mack Printing Company [ mark printing company ],1990, pages 1289-1329). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in therapeutic or pharmaceutical compositions is contemplated.
The phrase "pharmaceutically acceptable" as used herein refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
Generally, the term "pharmaceutical composition" is defined herein to mean a mixture or solution containing at least one therapeutic agent to be administered to a subject (e.g., mammal or human). The pharmaceutical combinations of the invention may be formulated into pharmaceutical compositions suitable for enteral or parenteral administration, such as those in unit dosage forms, for example sugar-coated tablets, capsules or suppositories or ampoules. If not otherwise indicated, these are prepared in a manner known per se, for example by means of various conventional mixing, comminuting, direct compression, granulating, sugar-coating, dissolving, lyophilizing processes or manufacturing techniques which are apparent to those skilled in the art. It will be appreciated that the unit content of the combination partner contained in the individual doses of each dosage form need not in itself constitute an effective amount, as the necessary effective amount can be achieved by administration of a plurality of dosage units. The pharmaceutical composition may contain from about 0.1% to about 99.9%, preferably from about 1% to about 60%, of one or more therapeutic agents. One of ordinary skill in the art can select one or more of the foregoing carriers by routine experimentation and without any undue burden as to the particular desired characteristics of the dosage form. The amount of each carrier used may vary within the conventional range in the art. The following references disclose techniques and excipients for formulating oral dosage forms. See The Handbook of Pharmaceutical Excipients [ handbook of pharmaceutical excipients ], 4 th edition, rowe et al, editions American Pharmaceuticals Association [ American society of pharmacies ] (2003); remington, the Science and Practice of Pharmacy [ leimington: science and practice of pharmacy ], 20 th edition, gennaro editions, lippincott Williams & Wilkins [ Wilkins publishing company ] (2003). These optional additional conventional carriers may be incorporated into the oral dosage form by incorporating one or more conventional carriers into the initial mixture prior to or during granulation, or by combining one or more conventional carriers with granules comprising the pharmaceutical agent combination or individual pharmaceutical agents of the pharmaceutical agent combination in the oral dosage form. In the latter embodiment, the combined mixture may be further blended, such as by a V-blender, and then pressed or molded into tablets (e.g., monolithic tablets), encapsulated, or filled into sachets. Obviously, the pharmaceutical combination of the present invention may be used for the manufacture of a medicament.
The present invention relates to such pharmaceutical combinations or pharmaceutical compositions, in particular for use as medicaments.
In particular, the combinations or compositions of the invention may be used to treat cancer.
The invention also relates to the use of the pharmaceutical combination or pharmaceutical composition of the invention for the preparation of a medicament for the treatment of cancer, and to a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical combination according to the invention or the pharmaceutical composition according to the invention.
As used herein, the term "treatment" includes treatment that alleviates, or mitigates at least one symptom in a subject, increases progression-free survival, overall survival, extends response duration, or delays disease progression. For example, the treatment may be to attenuate one or more symptoms of the disorder or to completely eradicate the disorder (e.g., cancer). Within the meaning of the present invention, the term "treatment" also means preventing, delaying the onset of the disease (i.e. the period of time before the clinical manifestation of the disease) and/or reducing the risk of developing or worsening the disease in a patient (e.g. a mammal, in particular a patient is a human). As used herein, the term "treatment" includes inhibition of tumor growth, which includes direct inhibition of primary tumor growth and/or systemic inhibition of metastatic cancer cells.
"subject," "individual," or "patient" are used interchangeably herein and refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, mice, apes, humans, farm animals, athletic animals, and pets.
The term "therapeutically effective amount" of a compound of the invention (e.g., a chemical entity or biological agent) refers to an amount of a compound of the invention that will elicit a biological or medical response (e.g., a decrease or inhibition of enzymatic or proteinaceous activity) in a subject, or that will ameliorate symptoms, alleviate a condition, slow or delay disease progression, or prevent disease, etc. In one embodiment, the in vivo therapeutically effective amount may be in the range of between about 0.1-500mg/kg, or between about 1-100mg/kg, depending on the route of administration.
As used herein, the term "inhibit" refers to a reduction or inhibition of a given condition, symptom or disorder, or disease, or a significant decrease in a baseline activity of a biological activity or process.
The optimal dose of each combination partner for treating cancer may be determined empirically for each individual using known methods and will depend on a variety of factors including, but not limited to: the extent of disease progression; age, weight, general health, sex, and diet of the individual; the time and route of administration; as well as other medications that the individual is taking. Conventional tests and procedures well known in the art may be used to determine the optimal dosage. The amount of each combination partner that can be combined with the carrier material to produce a single dosage form will vary depending upon the individual treated and the particular mode of administration. In some embodiments, a unit dosage form containing a combination of agents as described herein will contain each agent in the combination in an amount that is typically administered when the agents are administered alone.
The frequency of dosage may vary depending on the compound used and the particular condition to be treated or prevented. In general, it is preferred to use a minimum dose sufficient to provide effective therapy. The effectiveness of a patient's treatment can generally be monitored using assays appropriate for the condition being treated or prevented, which assays will be familiar to those of ordinary skill in the art.
As used herein, the term "TEAD-dependent cancer" refers to any cancer in which TEAD (i.e., TEAD1, TEAD2, TEAD3, and/or TEAD 4) or mutants or variants thereof are known to be related, for example, in cancers in which the Hippo pathway is genetically altered.
As used herein, the term "TEAD inhibitor" refers to a compound having activity as an inhibitor of TEAD (i.e., TEAD1, TEAD2, TEAD3, and/or TEAD 4) or a mutant or variant thereof, which can be measured in vitro, in vivo, or in a cell line. In examples, in the biochemical assays described in the examples, and/or in the reporter gene cell assays described in the examples, and/or in the proliferation cell assays described in the examples, IC 50 [μM]Is that<10, e.g. of<5, e.g<2, e.g. of<1, e.g. of<0.5, e.g<0.2, e.g <0.1。
The YAP/TAZ-TEAD protein-protein interaction inhibitors described herein refer to TEAD inhibitors that inhibit TEAD activity by inhibiting the interaction of YAP/TAZ complexes with TEAD. Superactivation of YAP/TAZ leading to TEAD activation has been reported in many cancers (e.g., malignant pleural mesothelioma). Inhibition of the interaction between YAP/TAZ and TEAD is therefore a promising mechanism for inhibiting TEAD activity.
Inhibitors of YAP/TAZ-TEAD protein-protein interactions of the invention include, but are not limited to, compounds of formula (I), the synthesis of which is described herein.
Wherein the method comprises the steps of
W is selected from O, and CH-R w ；
X is selected from CH, and N;
y is selected from CH, and N;
z is selected from CH 2 O, and NH;
wherein when Y is N, W is CH-R w And Z is O;
a is selected from
(i) Phenyl optionally substituted with: halogenating; or halogenated C 1 -C 3 An alkoxy group;
(ii) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, the aromatic heterocycle being optionally substituted by: a hydroxyl group; c (C) 1 -C 3 An alkoxy group; or oxo; and
(iii) A halogenated benzodioxole moiety having the formula:
R w selected from: (i) hydrogen; (ii) hydroxy; (iii) C (C) 1 -C 3 An alkoxy group; (iv) hydroxy-C 1 -C 3 An alkyl group; (v) C (C) 1 -C 3 An alkyl group; and (vi) C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group;
q is selected from: (i) -C (R) 7 ) 2 -N(R 8 )-R 1 The method comprises the steps of carrying out a first treatment on the surface of the (ii) A 9-or 10-membered partially saturated heteroaryl group containing at least one N heteroatom; and (iii) comprises a compound selected from N, O, S, -S (=o), and-S (=o) 2 A 4-, 5-, or 6-membered saturated heterocyclic ring of at least one heteroatom or heteroatom group, provided that at least one N heteroatom is present, wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from the group consisting of: hydroxy, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo and C 1 -C 3 Alkylene groups, which form a bridge between two ring atoms of a saturated heterocyclic ring, thereby forming a bridged bicyclic structure;
R 1 selected from: (i) hydrogen; (ii) C (C) 1 -C 6 Alkyl, optionally deuterated; and (iii) (CH 2 ) 0-2 R 1a ；
R 1a Selected from: (i) Hydroxy C 1 -C 4 An alkyl group; (ii) C (C) 1 -C 3 An alkoxy group; (iii) A 5-or 6-membered saturated heterocyclic ring comprising at least one heteroatom selected from N and O, the saturated heterocyclic ring optionally being independently substituted one or more times by: c (C) 1 -C 3 An alkyl group; (CH) 2 ) 0-1 C (O) di (C) 1 -C 3 Alkyl) amino; SO (SO) 2 C 1 -C 3 An alkyl group; c (O) C 1 -C 3 An alkyl group; or oxo; (iv) C (C) 3 -C 6 Cycloalkyl optionally substituted one or more times independently with: a hydroxyl group; hydroxy C 1 -C 4 An alkyl group; c (C) 1 -C 6 An alkoxy group; c (O) OC 1 -C 3 An alkyl group; CO 2 H；SO 2 C 1 -C 3 An alkyl group; halogenated C 1 -C 3 An alkyl group; NHR (NHR) 1b ；(CH 2 ) 0-1 C(O)NR 1c R 1d ；C 1 -C 6 An alkyl group; halogenated C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group; halogenating; 5-or 6-membered aromatic heteroatomic containing at least one heteroatom selected from N, O, and SA ring; or two R 1e The group(s) is (are) a radical,
wherein two R's attached to the same carbon atom 1e Together with the carbon atom to which they are attached, form a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or C 3 -C 6 Cycloalkyl, the saturated heterocycle or cycloalkyl being optionally substituted with: hydroxy or oxo;
R 1b selected from: (i) C (O) C 1 -C 3 An alkyl group; and (ii) SO 2 C 1 -C 3 An alkyl group;
R 1c and R is 1d Each independently selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; and (iii) hydroxy C 1 -C 4 An alkyl group;
R 2 selected from: (i) hydrogen; and (ii) halo;
R 3 selected from: (i) halo; (ii) Halogenated C 1 -C 3 An alkyl group; and (iii) cyano;
R 4 selected from: (i) hydrogen; (ii) halo; and (iii) C 1 -C 3 An alkyl group;
R 5 selected from: (i) hydrogen; (ii) C (C) 1 -C 6 Alkoxy optionally substituted with: c (C) 3 -C 6 Cycloalkyl; CO 2 H；SO 2 C 1 -C 3 An alkyl group; a 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; or a 5-or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally being C (O) C 1 -C 3 Alkyl substitution;
(iii) Halogenating; (iv) Hydroxy C 1 -C 6 An alkoxy group, wherein the alkoxy group is optionally deuterated; (v) Halo C optionally substituted with hydroxy 1 -C 6 An alkoxy group; (vi) S-halo C optionally substituted with hydroxy 1 -C 3 An alkyl group; (vii) C (C) 1 -C 3 Alkoxy C 1 -C 3 An alkoxy group; (viii) NR (NR) 5a R 5b ；(ix)C 1 -C 3 An alkyl group; (x) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; and (xi) hydroxy;
R 5a and R is 5b Each independently selected from: (i) hydrogen; and (ii) C 1 -C 3 An alkyl group;
or alternatively
R 5a And R is 5b Together with the nitrogen atom to which they are attached, form a 5-or 6-membered saturated heterocyclic ring, which optionally additionally carries a hydroxyl group;
R 6 selected from: (i) hydrogen; (ii) cyano; (iii) C (O) NHR 6a ；(iv)NHR 6b The method comprises the steps of carrying out a first treatment on the surface of the And (v) NH 2 Or hydroxy-substituted C 1 -C 3 An alkoxy group;
R 6a selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; (iii) C (C) 3 -C 6 Cycloalkyl; (iv) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, the aromatic heterocycle being optionally substituted by: c (C) 1 -C 3 An alkyl group;
R 6b is covered by NH 2 Or hydroxy-substituted C 1 -C 3 An alkyl group;
R 7 each independently selected from hydrogen and C 1 -C 3 An alkyl group; and
R 8 is hydrogen or C 1 -C 3 -an alkyl group.
In embodiments, the compound of formula (I) or a pharmaceutically acceptable salt thereof has formula (Ia), (Ic) or (Id),
in embodiments, X is selected from CH, and N;
a is selected from
(i) Phenyl optionally substituted with: halogenating; or halogenated C 1 -C 3 An alkoxy group;
(ii) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, preferably selected from N and S, the aromatic heterocycle being optionally substituted by: a hydroxyl group; c (C) 1 -C 3 An alkoxy group; or oxo; and
(iii) A halogenated benzodioxole moiety having the formula:
R w selected from: (i) hydrogen; (ii) hydroxy; (iii) C (C) 1 -C 3 An alkoxy group; (iv) hydroxy-C 1 -C 3 An alkyl group; (v) C (C) 1 -C 3 An alkyl group; and (vi) C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group;
q is selected from: (i) -C (R) 7 ) 2 -N(R 8 )-R 1 The method comprises the steps of carrying out a first treatment on the surface of the (ii) A 9-or 10-membered partially saturated heteroaryl group containing at least one N heteroatom; and (iii) a 4-, 5-, or 6-membered saturated heterocyclic ring comprising at least one heteroatom selected from N, O and S, provided that at least one N heteroatom is present, and wherein the N is optionally present in the alpha position of the atom that binds Q to the remainder of the molecule, and wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from: hydroxy, C 1 -C 3 Alkyl, C 1 -C 3 Alkoxy, halo, and methylene groups, which form a bridge between two ring atoms of a saturated heterocyclic ring, thereby forming a bridged bicyclic structure;
R 1 selected from: hydrogen; c (C) 1 -C 6 An alkyl group; and (CH) 2 ) 0-2 R 1a Wherein
R 1a Selected from: (i) C (C) 1 -C 3 An alkoxy group; (ii) C (C) 3 -C 6 Cycloalkyl optionally substituted one or more times independently with: a hydroxyl group; hydroxy C 1 -C 4 An alkyl group; c (C) 1 -C 4 An alkoxy group; c (O) OC 1 -C 3 An alkyl group; CO 2 H；C(O)NR 1c R 1d ；C 1 -C 6 An alkyl group; halogenating; halogenated C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group; SO (SO) 2 C 1 -C 3 An alkyl group; halogenated C 1 -C 3 An alkyl group; NHR (NHR) 1b ；C(O)NR 1c R 1d The method comprises the steps of carrying out a first treatment on the surface of the A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S; or two R 1e A group wherein the two R' s 1e The groups being attached to the same carbon atom and together with the carbon atom to which they are attached forming a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or C 3 -C 6 Cycloalkyl, the saturated heterocycle or cycloalkyl being optionally substituted with: hydroxy or oxo; (iii) A 5-or 6-membered saturated heterocyclic ring comprising at least one heteroatom selected from N and O, the saturated heterocyclic ring optionally being independently substituted one or more times by: c (C) 1 -C 3 An alkyl group; (CH) 2 ) 0-1 C (O) di (C) 1 -C 3 Alkyl) amino; SO (SO) 2 C 1 -C 3 An alkyl group; c (O) C 1 -C 3 An alkyl group; or oxo;
R 1b selected from C (O) C 1 -C 3 Alkyl, and SO 2 C 1 -C 3 An alkyl group;
R 1c and R is 1d Each independently selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; and (iii) hydroxy C 1 -C 4 An alkyl group, a hydroxyl group,
R 2 is hydrogen or halogen, and the halogen is substituted,
R 3 is halogenated, halogenated C 1 -C 3 An alkyl group, or a cyano group,
R 4 selected from: hydrogen; halogenating; and C 1 -C 3 An alkyl group, a hydroxyl group,
R 5 selected from: (i) hydrogen; (ii) halo-C optionally substituted with hydroxy 1 -C 6 An alkoxy group; (iii) S-halo C optionally substituted with hydroxy 1 -C 3 An alkyl group; (iv) C (C) 1 -C 3 Alkoxy C 1 -C 3 An alkoxy group; (v) C (C) 1 -C 6 Alkoxy optionally substituted with: SO (SO) 2 C 1 -C 3 Alkyl, C 3 -C 6 Cycloalkyl, CO 2 H. Or a 5-or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally being C (O) C 1 -C 3 Alkyl substitution; (vi) C (C) 1 -C 3 An alkyl group; (vii) Hydroxy C 1 -C 6 An alkoxy group; (viii) A 5-or 6-membered aromatic heterocycle comprising at least one heteroatom, preferably at least one N heteroatom, selected from N, O, and S; and (ix) a hydroxyl group,
R 6 is cyano; c (O) NHR 6a ；NHR 6b The method comprises the steps of carrying out a first treatment on the surface of the Or by NH 2 Or hydroxy-substituted C 1 -C 3 An alkoxy group, an amino group,
R 6a selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkyl group; (iii) C (C) 3 -C 6 Cycloalkyl; and (iv) a 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S, preferably at least one N heteroatom, the aromatic heterocycle being optionally substituted by: c (C) 1 -C 3 An alkyl group;
R 6b is covered by NH 2 Or hydroxy-substituted C 1 -C 3 An alkyl group;
R 7 each independently selected from hydrogen and C 1 -C 3 Alkyl group, and
R 8 is hydrogen or C 1 -C 3 An alkyl group.
In embodiments, X is selected from CH, and N;
a is phenyl optionally substituted with: halogenating; or halogenated C 1 -C 3 An alkoxy group;
R w selected from: (i) hydrogen; (ii) C (C) 1 -C 3 An alkoxy group; (iii) hydroxy-C 1 -C 3 An alkyl group; (iv) C (C) 1 -C 3 An alkyl group; and (v) C 1 -C 3 alkoxy-C 1 -C 3 An alkyl group;
q is selected from: (i) -C (R) 7 ) 2 -NH-R 1 The method comprises the steps of carrying out a first treatment on the surface of the And (ii) a 4-, 5-, or 6-membered saturated heterocyclic ring comprising one or two heteroatoms independently selected from N, O and S, provided that at least one N heteroatom is present, wherein the N is present in the alpha position of the atom that binds Q to the remainder of the molecule, and wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from: hydroxy, C 1 -C 3 Alkyl and halo;
R 1 selected from: (i) C (C) 1 -C 6 An alkyl group; and (ii) R 1a The method comprises the steps of carrying out a first treatment on the surface of the Wherein the method comprises the steps of
R 1a Selected from C 3 -C 6 Cycloalkyl optionally substituted one or more times independently with: a hydroxyl group; c (C) 1 -C 6 An alkyl group; or halogenated;
R 2 is hydrogen or halo;
R 3 is halogenated,
R 4 Selected from: (i) hydrogen; and (ii) halo;
R 5 selected from: halo-C 1 -C 6 Alkoxy, hydroxy, C 1 -C 6 An alkoxy group; and hydroxy C 1 -C 6 An alkoxy group;
R 6 is C (O) NHR 6a ；
R 6a Selected from: (i) hydrogen; and (ii) C 1 -C 3 An alkyl group;
and is also provided with
R 7 Each independently selected from hydrogen and C 1 -C 3 An alkyl group.
In embodiments, X is selected from CH, and N;
a is phenyl optionally substituted with: halogenating; or halogenated C 1 -C 3 Alkoxy, especially unsubstituted phenyl;
R w selected from: (i) hydrogen; and (ii) C 1 -C 3 An alkyl group, a hydroxyl group,
q is selected from: (i) -C (R) 7 ) 2 -NH-R 1 The method comprises the steps of carrying out a first treatment on the surface of the And (ii) a 4-, 5-, or 6-membered saturated heterocyclic ring comprising one or two heteroatoms independently selected from N and O, provided that at least one N heteroatom is present and is in the alpha position of the carbon atom that binds Q to the remainder of the molecule, wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from: hydroxy, C 1 -C 3 Alkyl and halo;
R 1 selected from: (i) C (C) 1 -C 6 An alkyl group; and (ii) R 1a The method comprises the steps of carrying out a first treatment on the surface of the Wherein the method comprises the steps of
R 1a Is C 3 -C 6 Cycloalkyl optionally substituted one or more times independently with: a hydroxyl group; c (C) 1 -C 6 An alkyl group; or halogenated;
R 2 is halo, especially fluoro;
R 3 is halo, especially chloro;
R 4 is halo, especially fluoro;
R 5 selected from: c (C) 1 -C 6 An alkoxy group; and hydroxy C 1 -C 6 An alkoxy group;
R 6 is C (O) NHR 6a ；
R 6a Selected from: (i) hydrogen; and (ii) C 1 -C 3 An alkyl group;
and is also provided with
Each R 7 Is hydrogen.
In embodiments, the compound of formula (I) is selected from the group consisting of:
(S) - (5-chloro-2, 4-diphenyl-2, 3-dihydrobenzofuran-2-yl) methylamine;
n1- (2- ((2S, 4S) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorophenyl) ethane-1, 2-diamine;
2- (2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorophenoxy) ethylamine;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 r) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-methylbenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-chlorobenzamide trifluoroacetate;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4-chloro-3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3, 4-difluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2S, 4S) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((R) -2-hydroxypropoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((R) -2-fluoropropoxy) benzamide;
2- (3- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4-carbamoyl-2-fluorophenoxy) acetic acid trifluoroacetate;
4- (((R) -4-acetylmorpholin-2-yl) methoxy) -2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
4- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6-methoxy nicotinamide;
4- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -6- (difluoromethoxy) -5-fluoronicotinamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (methylamino) benzamide;
2- ((2 s,4 s) -5-chloro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxy-N-methylbenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -N-cyclopropyl-3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3, 4-difluoro-N- (1-methyl-1H-pyrazol-5-yl) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxy-N- (pyridin-3-yl) benzamide;
2- ((2 s,4 s) -5-chloro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxy-N-methylbenzamide;
2- ((2 s,4 s) -5-chloro-2- (((trans-4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -5-chloro-2- (((cis-4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
(trans) -4- ((((2 s,4 s) -4- (6-carbamoyl-2-fluoro-3-methoxyphenyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-2-yl) methyl) amino) cyclohexanecarboxylic acid;
(cis) -4- ((((2 s,4 s) -4- (6-carbamoyl-2-fluoro-3-methoxyphenyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-2-yl) methyl) amino) cyclohexanecarboxylic acid;
2- ((2 r,4 s) -2- (aminomethyl) -5-chloro-2- (thiazol-4-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2- (2, 2-difluorobenzo [ d ] [1,3] dioxol-4-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2- (2-fluorophenyl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (cyclopropylmethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (1, 1-difluoro-2-hydroxyethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 r) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- ((1, 1-difluoro-2-hydroxyethyl) thio) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((methylsulfonyl) methoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (3, 3-difluoropropoxy) -3-fluorobenzamide;
4- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6-methoxy nicotinamide;
4- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) nicotinamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide;
4- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
4- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-methoxyethoxy) nicotinamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
4- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) nicotinamide;
2- ((2 s,4 s) -5-chloro-2- (((cyclopropylmethyl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide;
2- ((2S, 4S) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide;
4- ((2 s,4 s) -5-chloro-6-fluoro-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4- (methylsulfonyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4- (methylsulfonyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((4- (fluoromethyl) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (((4-acetaminocyclohexyl) amino) methyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((4- (methylsulfonyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- (((4- (dimethylcarbamoyl) cyclohexyl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((2-oxo-1-azaspiro [4.5] decan-8-yl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- (((1- (2- (dimethylamino) -2-oxoethyl) piperidin-4-yl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((4- (hydroxymethyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((3- (2-hydroxypropane-2-yl) cyclobutyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((1- (methylsulfonyl) piperidin-4-yl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -3- (hydroxymethyl) cyclobutyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -3- (hydroxymethyl) cyclobutyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-2- ((((2 r,4r,6 s) -2, 6-dimethyltetrahydro-2H-pyran-4-yl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-2- ((((2 r,4s,6 s) -2, 6-dimethyltetrahydro-2H-pyran-4-yl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
4- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6-methoxy nicotinamide;
4- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6-methoxy nicotinamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (((R) -tetrahydrofuran-2-yl) methoxy) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (((R) -tetrahydrofuran-2-yl) methoxy) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4-ethyl-3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4-ethyl-3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (1H-imidazol-1-yl) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (1H-imidazol-1-yl) benzamide;
2- ((2 s,4 s) -2- (((1-acetylpiperidin-4-yl) amino) methyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (pyrimidin-2-ylmethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (pyrimidin-2-ylmethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- ((tert-butylamino) methyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((R) -2-hydroxypropyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2S, 4S) -5-chloro-6-fluoro-2- ((((S) -1-hydroxypropan-2-yl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((1-methylcyclopropyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((2-methoxyethyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((2- (2-oxopyrrolidin-1-yl) ethyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -2- ((((trans) -4- (1H-tetrazol-1-yl) cyclohexyl) amino) methyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- (((trans-3- ((difluoromethoxy) methyl) cyclobutyl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((1 s,3r,4 r) -3-fluoro-4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((1 r,3s,4 s) -3-fluoro-4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((trans-3-fluorocyclobutyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((1 r,3 s) -3-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-1-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((6-hydroxy spiro [3.3] heptan-2-yl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 r,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 r,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2- (6-methoxypyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2- (2-methoxypyridin-3-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2- (2-oxo-1, 2-dihydropyridin-3-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-hydroxy-2- (2- (trifluoromethoxy) phenyl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -5-chloro-3-hydroxy-2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-3-hydroxy-2- ((((cis) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 r,3s,4 s) -5-chloro-3-hydroxy-2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 r,3s,4 s) -5-chloro-3-hydroxy-2- ((((cis) -4-hydroxycyclohexyl) amino) methyl) -2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -5-chloro-2- ((cyclobutylamino) methyl) -3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-2- ((cyclobutylamino) methyl) -6-fluoro-3-hydroxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-hydroxy-2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-hydroxy-2- ((((cis) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methoxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -3-methoxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxycyclohexyl) amino) methyl) -3-methoxy-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
4- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-methoxyethoxy) nicotinamide;
2- ((2 r,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 r,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 r,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide;
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide;
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- (((trans-4-hydroxycyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxycyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((cis) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- (((trans-4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- (((cis-4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-2- ((cyclobutylamino) methyl) -6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
4- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((trans-4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) nicotinamide;
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzonitrile;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- (((trans-4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide;
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide;
2- ((2S, 3S, 4S) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide;
2- (2- ((2 s,3s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3, 4-difluorophenoxy) ethan-1-ol;
2- ((2 r,3s,4 s) -5-chloro-6-fluoro-2- (6-hydroxypyridin-2-yl) -3-methyl-2- ((methylamino) methyl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 r,3s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2- (pyridin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2- (pyridin-3-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2 s,4 r) -2- (aminomethyl) -2-phenyl-5- (trifluoromethyl) -2, 3-dihydrobenzofuran-4-yl) -4-methoxybenzamide;
2- ((2 s,4 r) -5-cyano-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxy-N-methylbenzamide;
(S) -2- ((((trans) -4-hydroxycyclohexyl) amino) methyl) -2, 4-diphenyl-2, 3-dihydrobenzofuran-5-carbonitrile;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-2-phenyl-2, 3-dihydrofuro [2,3-b ] pyridin-4-yl) -3-fluorobenzamide;
2- (2- (aminomethyl) -6-chloro-2-phenyl-2, 3-dihydrobenzofuran-7-yl) -3-fluoro-4-methoxybenzamide;
2- (2- (aminomethyl) -5-chloro-2-phenylbenzo [ d ] [1,3] dioxol-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenylindolin-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- ((cyclohexylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-hydroxy-2- ((((cis) -4-methoxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-hydroxy-2- ((((trans) -4-methoxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
methyl (cis) -4- ((((2 s,4 s) -4- (6-carbamoyl-2, 3-difluorophenyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-2-yl) methyl) amino) cyclohexane-1-carboxylate;
methyl (trans) -4- ((((2 s,4 s) -4- (6-carbamoyl-2, 3-difluorophenyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-2-yl) methyl) amino) cyclohexane-1-carboxylate;
2- ((2 s,4 s) -2- ((((trans) -4-carbamoyl cyclohexyl) amino) methyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -2- ((((cis) -4-carbamoyl cyclohexyl) amino) methyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- ((((trans) -4- (methylcarbamoyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- ((((cis) -4- (methylcarbamoyl) cyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-2- ((((cis) -3- (difluoromethyl) cyclobutyl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -5-chloro-2- ((((trans) -3- (difluoromethyl) cyclobutyl) amino) methyl) -6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide;
2- ((2 s,4 s) -2- (aminomethyl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy-1, 2-d 4) -N-methylbenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((methyl-d 3) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide;
2- ((2 s,4 s) -5-chloro-6-fluoro-2- (((methyl-d 3) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy-1, 2-d 4) benzamide;
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
4- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide
2- ((2S, 3R, 4S) -5-chloro-6-fluoro-3- (methoxymethyl) -2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3R, 4S) -5-chloro-6-fluoro-3- (hydroxymethyl) -2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-2- ((((trans) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxy-2-methylpropyloxy) benzamide,
2- ((2S, 4S) -2- (azetidin-2-yl) -5-chloro-6-fluoro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide,
2- ((2S, 3S, 4S) -2- (azetidin-2-yl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide,
2- ((2S, 3S, 4S) -2- (azetidin-2-yl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide,
(2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide,
4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide,
2- ((4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-5- (methylcarbamoyl) pyridin-2-yl) oxy) acetic acid,
4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -5-fluoro-6-hydroxy-N-methylnicotinamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2- (4-hydroxypyrrolidin-2-yl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2- (4-hydroxy-4-methylpyrrolidin-2-yl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide,
(2S, 4R) -2- ((S) -5-chloro-6-fluoro-2, 4-diphenyl-2, 3-dihydrobenzofuran-2-yl) -4-fluoropyrrolidine,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -piperidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide,
(3- ((S) -5-chloro-6-fluoro-2, 4-diphenyl-2, 3-dihydrobenzofuran-2-yl) morpholine,
2- ((2S, 4S) -5-chloro-6-fluoro-2- (morpholin-3-yl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-hydroxy-2-phenyl-2- (pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methoxy-2-phenyl-2- (pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methoxy-2-phenyl-2- (pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide,
2- ((2S, 3S, 4S) -5-chloro-6-fluoro-3-methyl-2-phenyl-2- (pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide,
2- ((2S, 4S) -2- (1-aminoethyl) -5-chloro-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 3S, 4S) -2- (1-aminoethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- (2-methoxyethoxy) benzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) indolin-4-yl) -3-fluoro-4- (2-hydroxyethoxy) benzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) indolin-4-yl) -3-fluoro-4-methoxybenzamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) indolin-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) -N-methylbenzamide,
4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) indolin-4-yl) -5-fluoro-6- (2-hydroxyethoxy) -N-methylnicotinamide,
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide;
2- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxy-N-methylbenzamide; and
2- ((2S, 3S, 4S) -2- (aminomethyl) -5-chloro-6-fluoro-3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide or a pharmaceutically acceptable salt thereof.
In embodiments, the compound of formula (I) is />
In embodiments, the compound of formula (I) is
In embodiments, the compound of formula (I) isIn embodiments, the compounds of formula (I)The thing is->In an embodiment, the compound of formula (I) is +.>In an embodiment, the compound of formula (I) is +.>In an embodiment, the compound of formula (I) is +.>In an embodiment, the compound of formula (I) is +.>
In embodiments, the compound of formula (I) is/>
In embodiments, the compound of formula (I) is
In embodiments, the compound of formula (I) is
In an embodiment, the compound of formula (I) is (2P) -2- { (2S) -5-chloro-6-fluoro-2- [ (methylamino) methyl ] -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl } -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide, and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- [ (2S) -5-chloro-6-fluoro-2- ({ [ (1 r, 4S) -4-hydroxycyclohexyl ] amino } methyl) -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -4- (difluoromethoxy) -3-fluorobenzamide, and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- [ (2 s,3 s) -5-chloro-6-fluoro-3-hydroxy-2- ({ [ (1 r,4 s) -4-hydroxycyclohexyl ] amino } methyl) -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -4- (difluoromethoxy) -3-fluorobenzamide, and has the following structure:
In an embodiment, the compound of formula (I) is (2P) -2- [ (2S, 3S) -5-chloro-6-fluoro-2- ({ [ (1 r, 4S) -4-hydroxy-4-methylcyclohexyl ] amino } methyl) -3-methyl-2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -3-fluoro-4- [ (2S) -2-hydroxypropoxy ] benzamide and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- [ (2 s,3 s) -5-chloro-6-fluoro-2- ({ [ (1 r,4 s) -4-hydroxy-4-methylcyclohexyl ] amino } methyl) -3-methyl-2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -3-fluoro-4- (2-hydroxyethoxy) benzamide and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- [ (2S, 3S) -5-chloro-6-fluoro-2- ({ [ (1 r, 4S) -4-hydroxy-4-methylcyclohexyl ] amino } methyl) -3-methyl-2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -3-fluoro-4- [ (2S) -2-hydroxypropoxy ] benzonitrile and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- [ (2 s,3 s) -5-chloro-6-fluoro-2- ({ [ (1 r,4 s) -4-hydroxy-4-methylcyclohexyl ] amino } methyl) -3-methyl-2-phenyl-2, 3-dihydro-1-benzofuran-4-yl ] -3-fluoro-4- (2-hydroxyethoxy) -N-methylbenzamide, and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- { (2S, 3S) -5-chloro-6-fluoro-3-methyl-2- [ (methylamino) methyl ] -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl } -3-fluoro-4- [ (2S) -2-hydroxypropoxy ] -N-methylbenzamide, and has the following structure:
In an embodiment, the compound of formula (I) is (2P) -2- { (2 s,3 s) -5-chloro-6-fluoro-3-methyl-2- [ (methylamino) methyl ] -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl } -3-fluoro-4-methoxybenzamide and has the following structure:
in an embodiment, the compound of formula (I) is (4P) -4- { (2 s,3 s) -5-chloro-6-fluoro-3-methyl-2- [ (methylamino) methyl ] -2-phenyl-2, 3-dihydro-1-benzofuran-4-yl } -5-fluoro-6- (2-hydroxyethoxy) -N-methylpyridine-3-carboxamide, and has the following structure:
in an embodiment, the compound of formula (I) is (4P) -4- { (2S) -5-chloro-6-fluoro-2-phenyl-2- [ (2S) -pyrrolidin-2-yl ] -2, 3-dihydro-1-benzofuran-4-yl } -5-fluoro-6- (2-hydroxyethoxy) -N-methylpyridine-3-carboxamide and has the following structure:
in an embodiment, the compound of formula (I) is (2P) -2- { (2S) -5-chloro-6-fluoro-2-phenyl-2- [ (2S) -pyrrolidin-2-yl ] -2, 3-dihydro-1H-indol-4-yl } -3-fluoro-4- (2-hydroxyethoxy) benzamide and has the following structure:
/>
herein, the term compound F means
In this context, the term compound G means
Herein, the term compound D means
Herein, the term compound E means
Herein, the term compound A means />
Herein, the term compound H meansCompound H is also known as VT-104, CAS#2417718-25-1. Compounds of formula (I)The synthesis of H is described in WO 2020/097389.
In embodiments, the TEAD inhibitor is selected from the group consisting of: compound a, compound B, compound F, compound G, compound D, compound E, compound H, VT3989 (Vivace medical company (Vivace Therapeutics)), and tea inhibitors selected from those disclosed in WO 201753706, WO 2017064277, WO 2017058716, WO 2018185266, WO 2018204532, WO 2019040380, WO 2019113236, WO 2019171268, WO 2019222431, WO 2019232216, WO 2020097389, WO202014734, WO 2020051099, WO 2020243415, WO 2020243423, WO 2021097110, WO 2021102204, WO 2021133896, and WO 2022087008, and pharmaceutically acceptable salts thereof.
Each of WO 201753706, WO 2017064277, WO 2017058716, WO 2018185266, WO 2018204532, WO 2019040380, WO 2019113236, WO 2019171268, WO 2019222431, WO 2019232216, WO 2020097389, WO202014734, WO 2020051099, WO 2020243415, WO 2020243423, WO 2021097110, WO 2021102204, WO 2021133896 and WO 2022087008 and the TEAD inhibitors disclosed therein are incorporated by reference.
In embodiments, the TEAD inhibitor is selected from the group consisting of: compound a, compound B, compound F, compound G, compound D, compound E, compound H, VT3989 (Vivace healthcare), 3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one, (R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one, (S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one, (R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, (S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, (S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, (R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, (S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide, and pharmaceutically acceptable salts thereof.
In an alternative embodiment, the TEAD inhibitor isSuch inhibitors are disclosed in WO 2022/159986 and WO 2020/243415.
Some particularly preferred combinations include the following. According to another aspect of the present invention there is thus provided a method of treating cancer in a patient in need thereof, the method comprising administering to said patient any of the following combinations. According to a further aspect of the present invention there is thus provided any of the compounds listed in the following combinations for use in the treatment of cancer, wherein the treatment further comprises administration of other one or more combination partners.
Combination of two or more kinds of materials
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and a cMET inhibitor (e.g., carbamazepine or terponitinib, such as carbamazepine) or a pharmaceutically acceptable salt thereof
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KR) AS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb), and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical industry), JAB3312 (Gakesi pharmaceutical industry), RLY1971 (Roche company), SAR442720 (Sanofei corporation), RMC4550 (revolution pharmaceutical company), RMC4630 (revolution pharmaceutical company), BBP398 (Navire corporation), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Nanjing san Co., ltd.), PF0724982 (PY) ERAS601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical company), ICP189 (Nocheng Jianhua corporation), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical company), TAS-ASTX (Dapeng corporation) and tsukamu pharmaceutical Co., ltd (Taiho Co., ltd.)&Otsuka Pharmas&Otsuka Pharmas))、X-37-SHP2(X-37)、)
)/>
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldaxab, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxab)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib (neratinib), gefitinib, cetuximab, panitumumab (panitunib), lapatinib (lapatinib), dactinib (dacomitinib), cetuximab (necitumumab), nazatinib, LTT462 or vandetanib (vandetanib), such as LTT462 or erlotinib
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidarius, domperidone, du Weili Sib, april, or Erbuli, e.g., april)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimetinib, PD-0325901, and cobicitinib, e.g., trametinib)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof and MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirodelin))
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Nib, naprafenib, endoconfenib, vi Mo Feini, or Darafenib)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Nib, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
VT3989 (Vivace medical Co.) or a pharmaceutically acceptable salt thereof, and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, england Finnii, vitamin Mo Feini, or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
·Or a pharmaceutically acceptable salt thereof, and a cMET inhibitor (e.g., carbamazepine or teponinib, such as carbamazepine) or a pharmaceutically acceptable salt thereof
·Or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
·Or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS inhibitor or a KRAS inhibitor)
·Or a pharmaceutically acceptable salt thereof, an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additive manufacturing industry), JAB3312 (additive manufacturing industry), rle 1971 (roche company), SAR442720 (sirofine company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolutionary pharmaceutical company)Span), BBP398 (Navire corporation), BR790 (Shanghai blue and green medical science limited), SH3809 (nanjing holy & corporation), PF0724982 (pyro corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (norheng ku corporation), HBI2376 (hun subunit), ETS001 (shanghai yi tuo bio pharmaceutical corporation), TAS-ASTX (large peng corporation) and X-37-SHP2 (X-37), and the like > )
·Or a pharmaceutically acceptable salt thereof, and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sotoracicb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb)
·Or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib), or a pharmaceutically acceptable salt thereof
·Or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanite, aliquot)Larissin, copanide, du Weili sibutra, apicalide or Erbuli, e.g. apicalide)>
·Or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobicitinib, such as trametinib)
·Or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
·Or a pharmaceutically acceptable salt thereof, and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirodelin))
·Or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe west) or a pharmaceutically acceptable salt thereof
·Or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, encofilib, vitamin Mo Feini, or darafil)Nylon) of (1)>
·Or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, encouraging, vitamin Mo Feini, or dabrafen) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
·Or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound B or a pharmaceutically acceptable salt thereof, cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Compound B or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Compound B or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12/G13 inhibitor selected from the group consisting of Sotolacca, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotolacca, or adaglazeb) and a SHP2 inhibitor (e.g., a SHP2 inhibitor selected from the group consisting of TNO155, JAB3068 (Kochia), B3312 (Kochia), RLY1971 (Kochia) Company of Sauvignon), SAR442720 (Sauvignon company), RMC4550 (revolution pharmaceutical company), RMC4630 (revolution pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai Qing Yu Zhi medical science and technology Co., ltd.), SH3809 (Nanjing Sauvignon & Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical company), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Shangya), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )/>
)
Compound B or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound B or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound B or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalrisi, coumanesi, du Weili Sibutus, aprilst or Erbuli, e.g., april)
Compound B or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametetinib, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., trametetinib), or a pharmaceutically acceptable salt thereof
Compound B or a pharmaceutically acceptable salt thereof, and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound B or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirolimus))
Compound B or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound B or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
Compound B or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound B or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound a or a pharmaceutically acceptable salt thereof, cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Compound A or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Compound A or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12/G13 inhibitor selected from the group consisting of Sotolacca, aldaglaserib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., a compound C, sotolacca or Aldaglaserica) and a SHP2 inhibitor (e.g., a SHP2 inhibitor selected from the group consisting of TNO155, JAB 8 (GmbH), JAB3312 (GmbH), RLY1971 (Rongshi), 442720 (NosG 12C, RMC, JAB-21822, ASR-KRAS 12, ZKRAS 12C, NYU-12VC1, RMC6291 and SHP 2), pharmaceutical compositions (R-37, R-Ind), R-Ind (R-Ind) and R-Ind (R-Ind) may be included, R-Ind., )
Compound A or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (Innovative pharmaceutical Co., ltd.), RMC4630 (Innovative pharmaceutical Co., ltd.)) BBP398 (Navire Corp.), BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint He Corp.), PF0724982 (pyro Corp.), ERAS601 (Erasca Corp.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nucheng Jianhua Corp.), HBI2376 (Shangya Corp.), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng and Datsukamu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37), )
Compound A or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound a or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, rituximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound A or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalrisi, coumanesi, du Weili Sibutus, aprilst or Erbuli, e.g., april)
Compound A or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametetinib, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., trametetinib), or a pharmaceutically acceptable salt thereof
Compound A or a pharmaceutically acceptable salt thereof, and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound A or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirolimus))
Compound A or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound A or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
Compound a or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound A or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound D or a pharmaceutically acceptable salt thereof, cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Compound D or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Compound D or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12/G13 inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
Compound D or se:Sup>A pharmaceutically acceptable salt thereof and SHP2 inhibitor or se:Sup>A pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Canon, inc.), JAB3312 (Canon, inc.), RY 1971 (Roche Co.), SAR442720 (Sainofein Co., td.), RMC4550 (Ind. ), RMC4630 (Ind., td.), BBP398 (Navire Co., td.), BR790 (Shanghai Qing Yu, md., td.), SH3809 (Nanjing Saint Co., td.), PF0724982 (trim Co., jumcse:Sup>A), ERAS601 (Erascse:Sup>A Co., td.), RX-SHP2 (Redx Co., td.), ICP189 (Nocheng Jianhuse:Sup>A Co., td.), HBI2376 (Shanghai), ETS001 (Shanghai Yi Bio-Biopharmaceutical Co., td.), TAS-A)STX (Roc, katsukamu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37), )
Compound D or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound D or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, rituximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound D or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarios, coumarone, du Weili Sibution, aprilst, or Erbuli, e.g., april)
Compound D or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trimetinib, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., trimetinib), or a pharmaceutically acceptable salt thereof
Compound D or a pharmaceutically acceptable salt thereof, and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound D or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirolimus))
Compound D or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound D or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, napranafinib, encofenib, vitamin Mo Feini, or dabrafenib)
Compound D or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound D or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconcha, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound E or a pharmaceutically acceptable salt thereof, cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Compound E or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Compound E or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12/G13 inhibitor selected from the group consisting ofThe following salts: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB- )
Compound E or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Canon, inc.), JAB3312 (Canon, inc.), RLY1971 (Roche Co.), SAR442720 (Sainofein Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yu medicine technology Co., ltd.), SH3809 (Nanjing Co., ltd.), PF0724982 (Congo.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP189 (Noheng's Jianhua Co., ltd.), HBI2376 (Hu Asia Co., ltd.), ETS001 (Shanghai Yi Bio-Biopharmaceutical Co., ltd.), TAS-ASTX (Roc and Datsukamura pharmaceutical Co., ltd.), and X-37-SHP2 (X-37)) )
Compound E or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound E or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, spinetoram, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound E or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalalide, coumannide, du Weili Sibutus, aprilst or Erbuli, e.g., april)
Compound E or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametenib, bemetinib, semantenib, pimatinib, PD-0325901 and cobratinib, e.g., trametenib), or a pharmaceutically acceptable salt thereof
Compound E or a pharmaceutically acceptable salt thereof, and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11E, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound E or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid or hdm201 (also known as sirolimus))
Compound E or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound E or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
Compound E or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound E or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconcha, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11E, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound F (2- ((2S, 3S) -5-chloro-6-fluoro-2- ((((1 r, 4S) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide) or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamatinib or topotinib, e.g., carbamatinib)
Compound F or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof )
Compound F or a pharmaceutically acceptable salt thereof and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Canon, inc.), JAB3312 (Canon, inc.), RLY1971 (Roche Co.), SAR442720 (Sainofein Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yu medicine technology Co., ltd.), SH3809 (Nanjing Co., ltd.), PF0724982 (Congo.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP189 (Noheng's Jianhua Co., ltd.), HBI2376 (Hu Asia Co., ltd.), ETS001 (Shanghai Yi Bio-Biopharmaceutical Co., ltd.), TAS-ASTX (Roc and Datsukamura pharmaceutical Co., ltd.), and X-37-SHP2 (X-37)) )
Compound F or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound F or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, spinetoram, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound F or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidarios, coumarone, du Weili Sibution, aprilst, or Erbuli, e.g., april)
Compound F or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametetinib, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., trametetinib), or a pharmaceutically acceptable salt thereof
Compound F or a pharmaceutically acceptable salt thereof, and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound F or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid or hdm201 (also known as sirolimus))
Compound F or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound F or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
Compound F or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound F or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound G or a pharmaceutically acceptable salt thereof, cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Compound G or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Compound G or a pharmaceutically acceptable salt thereof (e.g., KRAS G12/G13 inhibitor selected from the group consisting of Sotolacca, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI 18)23911. AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotoraciclovir, or adaglazest), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
Compound G or a pharmaceutically acceptable salt thereof and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Canon, inc.), JAB3312 (Canon, inc.), RLY1971 (Roche Co.), SAR442720 (Sainofein Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yu medicine technology Co., ltd.), SH3809 (Nanjing Co., ltd.), PF0724982 (Congo.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP189 (Nocheng's Jianhua Co., ltd.), HBI2376 (Hu Asia Co., ltd.), ETS001 (Shanghai Yi Bio-Biopharmaceutical Co., ltd.), TAS-ASTX (Roc and Datsukamura pharmaceutical Co., ltd.), and X-37-SHP2 (X-37)) )
Compound G or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
Compound G or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, rituximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound G or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalalide, coumannide, du Weili Sibutus, aprilst or Erbuli, e.g., april)
Compound G or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametenib, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, e.g., trametenib), or a pharmaceutically acceptable salt thereof
Compound G or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Compound G or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid or hdm201 (also known as sirolimus))
Compound G or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
Compound G or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
Compound G or a pharmaceutically acceptable salt thereof and Raf inhibitors or pharmaceutically acceptable salts thereof (e.g., bei Fafei ni, naproxen, enkephalinib, vitamin Mo Feini or dabrafenib) and MEK inhibitors or pharmaceutically acceptable salts thereof (e.g., MEK inhibitors or pharmaceutically acceptable salts thereof selected from the group consisting of trametinib, bemetinib, semetinib, pimatetinib, PD-0325901 and cobicitinib, e.g., trametinib)
Compound G or a pharmaceutically acceptable salt thereof and Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconcha, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or teponinib, e.g., carbamazepine)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolaccb, adaglazeb, LY349446, D)-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and compound C, such AS compound C, sotoracicb or adaglazeb), and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikoku pharmaceutical industry), JAB3312 (jikesi pharmaceutical industry), RLY1971 (roc corporation), SAR442720 (cerofe corporation), RMC4550 (revolutionary pharmaceutical corporation), RMC4630 (revolutionary pharmaceutical corporation), BBP398 (Navire corporation), BR790 (Shanghai green light medical limited), SH3809 (nankingdom corporation), PF0724982 (pyro corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (nociception corporation), HBI2376 (hun biosciences), ETS001 (Shanghai Yi biosciences), tao biosciences (tao biosciences), tah (tao biosciences) and (taku corporation) 37-37 (shao-37) and (shao-37) )
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one and KRAS G12/G13 inhibitors or pharmaceutically acceptable salts thereof (e.g., KRAS G12C inhibitors selected from the group consisting of sotoracicb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and compound C, e.g., compound C, sotoracicb or adaglazeb)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, such as LTT462 or erlotinib)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirinotecan, idarubicin, copan, du Weili sibutra, aperturest, or erbelix, such as aperturest)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, such as trametinib)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib and abbe cilib or a pharmaceutically acceptable salt thereof
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, encofenib, vitamin Mo Feini, or dabrafenib)
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini or darifenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-032501 and cobratinib, such as tramatinib) or a pharmaceutically acceptable salt thereof
3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Ukephalli), JAB3312 (Ukephalli), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), SAR442720 (R.sub.C.) BR790 (Shanghai blue and white medical science Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (Congo Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nuchengjianhua Co., ltd.), HBI2376 (Shanghai Co., ltd.), ETS001 (Bio-pharmaceutical Co., ltd., hakka Yi Tuo Co., ltd.), TAS-ASTX (Roc, tukaki Co., ltd.), X-37-SHP2 (X-37), )
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikesi pharmaceutical industry), JAB3312 (jikesi pharmaceutical industry), RLY1971 (rogows corporation), SAR442720 (sainfield corporation), RMC4550 (revolutionary pharmaceutical corporation), RMC4630 (revolutionary pharmaceutical corporation), nap 398 (Navire corporation), BR790 (Shanghai qing pharmaceutical sciences corporation), SH3809 (nanjing holy & corporation), PF0724982 (part corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (nuo jian corporation), i2376 (hungry sub-biology), ETS001 (gakuda) and tsu corporation, hbs 001 (tao biosciences) and (sha 37-X, sha) and (shap 37-X) )
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolaccb, aldarac, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS 12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldarac)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, such as LTT462 or erlotinib)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarius, copanide, du Weili sibutril, aprilst, or Erbulicast, e.g., aprilprist)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, such as trametinib)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sireide))
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebamiphene and abbe cilib or a pharmaceutically acceptable salt thereof)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib)
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimecretinib, PD-032501 and cobicitinib, such as trametinib) or a pharmaceutically acceptable salt thereof
(R) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sotoracicb, adaglazeb, LY349446 or a pharmaceutically acceptable salt thereof)D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, such AS compound C, sotoracib, or adaglacib), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikesi pharmaceutical industry), JAB3312 (jikesi pharmaceutical industry), RLY1971 (rogows corporation), SAR442720 (sainfield corporation), RMC4550 (revolutionary pharmaceutical corporation), RMC4630 (revolutionary pharmaceutical corporation), nap 398 (Navire corporation), BR790 (Shanghai qing pharmaceutical sciences corporation), SH3809 (nanjing holy & corporation), PF0724982 (part corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (nuo jian corporation), i2376 (hungry sub-biology), ETS001 (gaku) and hbs-37-X (tax-37) and (sha 37-X) pharmaceutical corporation )
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolaccb, aldarac, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS 12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldarac)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, such as LTT462 or erlotinib)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarius, copanide, du Weili sibutril, aprilst, or Erbulicast, e.g., aprilprist)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, such as trametinib)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, or an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sireide))
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebamiphene and abbe cilib or a pharmaceutically acceptable salt thereof)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib)
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimecretinib, PD-032501 and cobicitinib, such as trametinib) or a pharmaceutically acceptable salt thereof
(S) -3-methyl-3- (5- (2- ((4- (trifluoromethyl) phenyl) amino) pyridin-3-yl) -1,3, 4-oxadiazol-2-yl) pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ing), BBP (NaP), BR (R.Chensin), BRL, R.Chensin), R.Chensin, R.3, R.Chensin.H. 3, R.Chensin.Chensin., X-37-SHP2 (X-37), )
)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilager, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilager or Aldaglazeb)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib beadab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enprefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, e.g., tramatinib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, aprilsedge, or Erbuli, e.g., aprilsedge)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinone or hdm201 (also known as sirodelin))
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Nib, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobicitinib, e.g., tramatinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitors or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
)/>
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilago, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., compound C, sotussilago or Aldaglazeb)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalrisis, copennisil, du Weili Sib, aprilius, or Erburilius, e.g., aprilius)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametetinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., trametenib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, aprilsedge, or Erbuli, e.g., aprilsedge)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinone or hdm201 (also known as sirodelin))
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Nib, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobicitinib, e.g., tramatinib)
N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitors or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxsulanib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, aprilsedge, or Erbuli, such as Aprilsedge)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ing), BBP (NaP), BR (R.Chensin), BRL, R.Chensin), R.Chensin, R.3, R.Chensin.H. 3, R.Chensin.Chensin., X-37-SHP2 (X-37), )
)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilago, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilago or Aldaglazeb)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib beadab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, aidoris, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib or a pharmaceutically acceptable salt thereof)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enprefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, e.g., tramatinib)
(R) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ing), BBP (NaP), BR (R.Chensin), BRL, R.Chensin), R.Chensin, R.3, R.Chensin.H. 3, R.Chensin.Chensin., X-37-SHP2 (X-37), )
)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilago, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilago or Aldaglazeb)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib beadab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, aidoris, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib or a pharmaceutically acceptable salt thereof)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enprefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobicitinib, e.g., tramatinib)
(S) -N- (4-hydroxybutan-2-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxsulanib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, aprilsedge, or Erbuli, such as Aprilsedge)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and CDK4/6 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., CDK4/6 inhibitor naphthamide selected from the group consisting of palbociclib, rebaudinib, and Abexinib
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof and the Raf inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthoamide naphthalenecarboxamide or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconcha, vitamin Mo Feini, or Darafenib) and MEK inhibitor naphthalenecarboxamide or a pharmaceutically acceptable salt thereof (e.g., MEK inhibitor naphthalenecarboxamide selected from the group consisting of trametinib, bemetinib, semantenib, pimatinib, PD-0325501, and cobratinib, such as trametinib)
(S) -N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthoamide naphthalenecarboxamide or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconcha, vitamin Mo Feini, or Darafenib) and ERK inhibitor naphthalenecarboxamide or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and the cMET inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, such as carbamazepine)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor naphthamide or a pharmaceutically acceptable salt thereof
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor naphthamide selected from the group consisting of: sotosilb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotosilb or adaglazeb), and SHP2 inhibitor naphthalamide or a pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor naphthalamide selected from the group consisting of TNO155, JAB3068 (Gakesipharmaceutical industry), JAB3312 (Gakesipharmaceutical industry), RLY1971 (Rogowski), 442720 (RMPhilin), RMC4550 (RMBB30), navig (R) (Navig), navig (SH) 790 (Navig), SAL), navig (Navig) 3 (Navig), SAL (Navig) 3, navig (Navig) or a pharmaceutically acceptable salt thereof Saint Co., ltd.), PF0724982 (Congo Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya Biometrics), ETS001 (Shanghai Yituo Biometrics Co., ltd.), TAS-ASTX (Roc and tsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37),)
)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthoamide naphthamide or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor naphthamide selected from the group consisting of Sotolaccb, adarag, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS 12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or adarag)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and the PI3K inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidoris, copanide, du Weili Sib, aprilsedge, or Erbuliusse, such as Aprilsedge)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthoamide naphthamide or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor naphthamide selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, the MDM2 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as siredelin))
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, such as tramatinib)
N- (1, 5-dihydroxypent-3-yl) -5- (4- (trifluoromethyl) phenoxy) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, such as carbamazepine)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: soto-placib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, soto-placib or adaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salts thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salts thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Roche), SAR442720 (Nofei), RMC4550 (Ming., drug), RMC4630 (revolution), BBP (NaP), BR (R.9, R.E.Chemie), R.3, R.J. 3, R. SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Roc Co., ltd.), X-37-SHP2 (X-37), a process for producing the same,)
)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotosituba, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaglazeb)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, rituximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, domperidone, du Weili sibutril, apicalist, or Erbuli, e.g., apicalicheat)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametenib, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, such as trametenib)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirolimus))
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebamipiclib, and abbe cilib
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, such as tramatinib)
N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gastrongylus), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ind), BBP (NaP), BR (R.Ind., R.Chensin), R.37-F), R.37, R.Ing., R.Tsakunski 37-F), R.Ing., R.Tsaku., )
)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldarasib)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarrisi, domonan, du Weili siban, april, or Erbuli plug, e.g., april)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encomanil, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
8-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ing), BBP (NaP), BR (R.Chensin), BRL, R.Chensin), R.Chensin, R.3, R.Chensin.H. 3, R.Chensin.Chensin., X-37-SHP2 (X-37), )
)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldarasib)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarrisi, domonan, du Weili siban, april, or Erbuli plug, e.g., april)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobicitinib, e.g., tramatinib)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salt, or its pharmaceutically acceptable salt (e.g., bei Fafei Ni, naprafenib, encomanil, vitamin Mo Feini, or Darafenib) and MEK inhibitor or its pharmaceutically acceptable salt (e.g., MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, e.g., trametinib)
8-amino-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, such as carbamazepine)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N-isopropyl-8-methyl-5- [4- (trifluoromethyl)Radical) phenyl]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gastrongylus), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ind), BBP (NaP), BR (R.Ind., R.Chensin), R.37-F), R.37, R.Ing., R.Tsakunski 37-F), R.Ing., R.Tsaku., )/>
)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolla)Sibirica or adaglazeb) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or Aldax)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edally, coumannide, du Weili Sib, april or Erbuli plug, such as April)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
N-isopropyl-8-methyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., selected from the group consisting ofKRAS G12C inhibitors or pharmaceutically acceptable salts thereof: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldarabib)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edally, coumannide, du Weili Sib, april or Erbuli plug, such as April)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
8-ethyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolacia, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, KRAS G12C, KRAS-G12/G13) inhibitor or a pharmaceutically acceptable salt thereof,AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb), and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi pharmaceutical Co.), JAB3312 (Jiakeshi pharmaceutical Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., ltd.), BBP398 (Navire Co.), BR790 (Shanghai Green medical science and technology Co., ltd.), SH3809 (Nanjing & Co., ltd.), PF0724982 (Erras, ehrub Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nuhong Jianhua Co., ltd.), HBI2376 (Shanghai Yi Bio Co., ltd.), TAS-ASTAX (Dapeng & Datsuki Co., ltd.) and X-37-SHP (SHP-37))
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalteus, coumannide, du Weili Sibutine, april, or Erburil plug, e.g., april)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enc Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
8-cyclopropyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoro)Methyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Conduca Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37))
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolacca, adaxab, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or adaxab)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib or a pharmaceutically acceptable salt thereof)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, such as tramatinib)
8-amino-7-bromo-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gastrongylus), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ind), BBP (NaP), BR (R.Ind., R.Chensin), R.37-F), R.37, R.Ing., R.Tsakunski 37-F), R.Ing., R.Tsaku., )
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additive manufacturing industry), JAB3312 (additive manufacturing industry), RLY1971 (roche company), SAR442720 (sirofine company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolution)Pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (trim Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nuhong Jianhua Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.) and X-37-SHP2 (X-37),)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldarabib)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edally, coumannide, du Weili Sib, april or Erbuli plug, e.g., april)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
7-bromo-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotussian, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotussian or Alglaglaglazeb) and SHP2 inhibitor or pharmaceutically acceptable salt thereof (e.g., SHP2 inhibitor or pharmaceutically acceptable salt thereof selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Rogown), SAR (Nofei), RMC4550 (Ming pharmaceutical), RMC4630 (Ing), BBP (NaP), BR (R.Chensin), BRL, R.Chensin), R.Chensin, R.3, R.Chensin.H. 3, R.Chensin.Chensin., X-37-SHP2 (X-37), )
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakesi pharmaceutical), JAB3312 (Jiakesi pharmaceutical), RLY1971 (Roche), SAR442720 (Sanofei Corp.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Corp.), BR790 (Shanghai Qing medical science Co., ltd.), SH3809 (Navigor Co.), PF0724982 (Ju.), ERAS601 (Erasca Corp.), RX-SHP2 (Redx pharmaceutical), ICP189 (Nuhon Chen Cheng Session), HBI2376 (Shanghai Hill Biol.), ETS001 (Shanghai ETY Bio Ind.), TAS-ASTX (Dai Peng and X37-SHP 37-37 and SHP-37))
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolacca, adaxab, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or adaxab)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelinib, or a pharmaceutically acceptable salt thereof)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, such as tramatinib)
8-amino-7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotosib, adagransieb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotosia or adagransieb), and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., SHP2 inhibitors selected from the group consisting of TNO155, JAB3068 (Gakesii pharmaceutical industry), JAB3312 (Gakesii pharmaceutical industry), RLY1971 (Roche), SAR442720 (Nofei pharmaceutical), RMC4550 (Ming pharmaceutical), RMC4630 (Ind), BBP (NaLevone), BRR (Navjingsu) and SHP 3, SHP2 inhibitors or pharmaceutically acceptable salts thereof (including TNO155, JAB3068 (Gastrongkeside pharmaceutical industry), JAB3312 (Gastrongpoint pharmaceutical industry), JA 3800, SANJ 3312 (Nakeside pharmaceutical Co., RLY1971 (Nakeside), SAL 3, SALv 3, SAL 3, SAL 3068, SAL 2 inhibitor or pharmaceutically acceptable salts thereof Company), PF0724982 (pyro), ERAS601 (Erasca), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya Biometrics), ETS001 (Shanghai Yituo Biometrics Co., ltd.), TAS-ASTX (Dapeng and Datsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37),)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi pharmaceutical Co.), JAB3312 (Jiakeshi pharmaceutical Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., ltd.), BBP398 (Navire Co.), BR790 (Shanghai green, medical science Co., ltd.), SH3809 (Nanj & Co.), PF0724982 (Hu Co., ltd.), ERAS601 (Erasc Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nohong's, ind.), HBI2376 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-AST (Dapeng and Datsuk Co., ltd.), and X-37-SHP (SHP-37))
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldarasib)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarrisi, domonan, du Weili siban, april, or Erbuli plug, e.g., april)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encomanil, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
7-chloro-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of sotoraciclovir, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and a compound C, such AS compound C, sotoraciclovir or adaglazeb) and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of TNO155, JAB3068 (Gakesi pharmaceutical industry), JAB3312 (Gakesi pharmaceutical industry), RLY1971 (Roche company), SAR442720 (Sanofei company), RMC4550 (revolution pharmaceutical company), RMC4630 (revolution pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), ETS001 (Shanghai Yi Tu Kao Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37) )
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or Aldax)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalisil, coumannide, du Weili Sib, april or Erbuli plug, e.g., april)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
N-isopropyl-8-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, such as carbamazepine)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., selected from the group consisting ofA KRAS G12C inhibitor of group or a pharmaceutically acceptable salt thereof: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or Aldax)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalisil, coumannide, du Weili Sib, april or Erbuli plug, e.g., april)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
N-isopropyl-7-methoxy-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical industry), JAB3312 (Gakesi pharmaceutical industry), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Innovative pharmaceutical Co.), RMC4630 (Innovative pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai blue) of Shanghai Qingyo medical science, inc.), SH3809 (Nanjing Sanhome), PF0724982 (trim Co.), ERAS601 (Erasca Co.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Shangya Co.), ETS001 (Shanghai Yituo Bio-pharmaceutical Co.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), TAS-ASTX (Darcy Katsuki pharmaceutical Co., ltd.), )
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additionally Korea), JAB3312 (additionally Korea), RLY1971 (Roche), SAR442720 (Sanofei Corp.), RMC4550 (Innovative Corp.), RMC4630 (Innovative pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (Congo Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nucheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.) and X-37-SHP2 (X-37),)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolaccb, aldaxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldaxib)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarios, domonan, du Weili siban, april, or Erbuli plug, e.g., april)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobicitinib, e.g., tramatinib)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encomanil, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N-isopropyl-7-methyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldarabine, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or Aldarabine)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxetinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edally, coumannide, du Weili Sibutine, april or Erbutil, e.g., april)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idaverine (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, endoconcha, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
7-cyclopropyl-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, such as carbamazepine)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotosib, adagransieb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC C, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS compound C, sotosib or adagransieb, and SHP2 inhibitors (e.g., SHP2 inhibitors selected from the group consisting of TNO155, JAB3068 (Gakesi), JAB3312 (Gakesi), RLY1971 (Roche), SAR442720 (Nofei), C4550 (Ming), RMC4630 (Ming), BBP398 (Navire), BR (Shanghai medical limited), and SHP2 inhibitors (e.g., SHP2 inhibitors) ) SH3809 (Nanjing Saint Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.) HBI2376 (Huya organism), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Roc and Datsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacca, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacca or Aldarabib)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalisil, coumannide, du Weili Sib, april or Erbuli plug, such as April)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enc-Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
7-amino-N-isopropyl-5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Soto-taraxlebox, aldarasicloth, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KR) AS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoraciclovir, or adaglaciclovir), and an inhibitor of SHP2 (e.g., an inhibitor of SHP2 selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi pharmaceutical Co.), JAB3312 (Jiakeshi pharmaceutical Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., ltd.), BBP398 (Navire Co.), BR790 (Shanghai green, medical science Co., ltd.), SH3809 (Nanj & Co.), PF0724982 (Hu Co., ltd.), ERAS601 (Erasc Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nohong's, ind.), HBI2376 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-AST (Dapeng and Datsuk Co., ltd.), and X-37-SHP (SHP-37) )
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldarasib)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarrisi, domonan, du Weili siban, april, or Erbuli plug, e.g., april)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encomanil, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
7-ethyl-N-isopropyl-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (1, 3-dihydroxypropane)-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakesi pharmaceutical Co., ltd.), JAB3312 (Jiakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Sanofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai's medical science Co., ltd.), SH3809 (Nasan Co., ltd.), PF0724982 (Ju.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nuo Chensin, HBI2376 (Shanghai, shanghai) and ETS001 (Shanghai biopharmaceutical Co., ltd.), TAS-X (Dairy.))Peng and Katsukamu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37),)
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12/G13, SF KRAS G12/G13, RMC032, JAB-21822, AST-KRAS G12/G13, MRTX1257, AZ KRAS G12/G13, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldaglazeb)
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, wei Mo Feini, or Darafenib)
N- (1, 3-dihydroxypropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, such as tramatinib)
N- (1, 3-dihydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthaceneAmide or a pharmaceutically acceptable salt thereof, and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikusi pharmaceutical), JAB3312 (jikusi pharmaceutical), rle 1971 (rogowski), SAR442720 (senofie corporation), RMC4550 (revolutionary pharmaceutical), RMC4630 (revolutionary pharmaceutical), BBP398 (Navire corporation), BR790 (Shanghai green medical science and technology limited), SH3809 (nanking & corporation), PF0724982 (fei corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (norheng healthcare corporation), HBI2376 (hun subunit), ETS001 (shanghai yi bio-pharmaceutical corporation), TAS-ASTX (da and tsukamurella) and X-37-SHP2 (X-37),)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilago, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilago or Aldaglazeb)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib beadab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethine, edalrisil, coumanesil, du Weili Sib, aprilst, or Erbutilide, e.g., aprilprist)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
(R) -N- (1-aminopropane-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: soto-Laxib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC C, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS compound C, soto-Laxib or adaglazeb, and SHP2 inhibitor (e.g., SHP2 inhibitor selected from the group consisting of TNO155, JAB3068 (Gakesi), JAB3312 (Gakesi), RLY1971 (Roche), SAR442720 (Nofei), C4550 (Ming), RMC4630 (Ming), bivine), BBP398 (Navire), BR (Shanghai), uighur medicine, ERS (ERGY) 790 (Ercin) and Rdset al, R-3 (R-Kappy), R-Kappy, and Sh (Sh), R-Kappy 2, sh 2 inhibitor (e.g., sh-Sh), sh 2 inhibitor (e.g., sh-Sh 2 inhibitor) 189 (Nochengjianhua corporation), HBI2376 (Huya organism), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Roc, dai Katsujo pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Conduca Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37))
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilager, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilager or Aldaglazeb)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib beadab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofeniil, wei Mo Feini, or Darafenib)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enprefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, e.g., tramatinib)
(S) -N- (1-hydroxypropan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotosib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G 12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb) and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Conduca Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37) )
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacia or adaglazeb
(R) -N- (1-hydroxypropane-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of: trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of: palbociclib, rebamiphene and abbe's west ib
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofeniil, wei Mo Feini, or Darafenib)
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naprafenib, encofenib, vitamin Mo Feini, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of: trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
(R) -N- (1-hydroxypropan-2-yl) -5- (4-trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Gakesi pharmaceutical Co.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qing Ku medical science Co., ltd.), SH3809 (Nanjin & Co.), PF0724982 (Juy Co.), ERAS601 (Erasca Co.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Shanghai Asia organism), ETS001 (Shanghai Yiyi biosome)Pharmaceutical Co.), TAS-ASTX (Roc, katsukamu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37),)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldax)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxcetirib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethi, aidaris, domonan, du Weili Sib, april, or Erbuli, e.g., april)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobicitinib, e.g., trametinib)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, MDM2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirodelin))
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salts, or Raf inhibitors or its pharmaceutically acceptable salts (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and MEK inhibitors or its pharmaceutically acceptable salts (e.g., MEK inhibitors selected from the group consisting of trametinib, bemetinib, semtinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
N- (2-hydroxyethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitors or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini or Darafenib) and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sainofei Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy Co.), ERAS601 (Erasca Co.), SHP2 (Redx Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Huya Co.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), and Ts, X-37-SHP2 (X-37), )
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and an inhibitor of SHP2 or a pharmaceutically acceptable salt thereofFor example, TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Sanofei Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Ji medical science Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (Bugine Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37),)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotussilago, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., compound C, sotussilago or Aldaglazeb)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, edalrisis, copennisil, du Weili Sib, aprilius, or Erburilius, e.g., aprilius)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametetinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., trametenib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib or a pharmaceutically acceptable salt thereof)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
(S) -N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotosib, adagransieb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC C, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS compound C, sotosia or adagransieb, and SHP2 inhibitors (e.g., SHP2 inhibitors selected from the group consisting of TNO155, JAB3068 (Gakesi), JAB3312 (Gakesi), RLY1971 (Roche), SAR442720 (Nakefir), C4550 (R, RMC 4630), BBP398 (Navirre), BR (Shanghai medicine), well AS Kogynectar, R790 (R), R.Ind.Chemical), R.Ind. ETS001 (Hashimoto Bio-pharmaceutical Co., ltd.), TAS-ASTX (Roc, dai Katsujo pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi Co., ltd.), JAB3312 (Jiakeshi Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Safeofie Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai's medical science Co., ltd.), SH3809 (Navigor Co., ltd.), PF0724982 (Hu Co., ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP (Nohon Jian.), HBI2376 (Shanghai Biometrics), ETS001 (Shanghai) biological pharmaceutical Co., ltd.), TAS-X (Dapeng and Datsuk and X37-37 (SHP-37 Co., ltd.)))
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, aprilius or Erbuli, e.g., aprilius)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinone or hdm201 (also known as sirodelin))
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901 and cobratinib, e.g., tramatinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, raf inhibitors or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRASG12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and compound C, such as compound C, sotoracicb or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi), JAB3312 (Jiakeshi), RLY1971 (Roche Co.), SAR442720 (Safeofe Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qing, medical science Co., ltd.), SH3809 (Nanj Saint Co.), PF0724982 (Huy Co.), ERAS601 (Erasca Co.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong's, ind.), HBI2376 (Hu's, ind.), ETS001 (Shanghai Yi Bio-Biometrics), S-ASTX (Dapeng., ltd.), TAP-AST (Datsuk Co., ltd.), and SHP-37 (SHP-37))
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacia or adaglazeb
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, apilimus, or ependymal, such as apilimus)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of: trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of: palbociclib, rebamiphene and abbe's west ib
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, encofenib, vitamin Mo Feini, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of: trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
(R) -N- (1-6-aminopyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a cMET inhibitor, or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor, or a pharmaceutically acceptable salt thereof
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additive manufacturing), JAB3312 (additive manufacturing), RLY1971 (roche company), SAR442720 (sirofine company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolutionary pharmaceutical company)Span), BBP398 (Navire Corp.), BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint He Corp.), PF0724982 (pyro Corp.), ERAS601 (Erasca Corp.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nuhong Jianhua Corp.), HBI2376 (Shangya Corp.), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.) and X-37-SHP2 (X-37),)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolaccb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or adaglazeb)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, EGFR inhibitors, or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxsulab, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidaris, coupannix, du Weili Sib, april, or Erbuli, e.g., april)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, ERK inhibitors, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib, or a pharmaceutically acceptable salt thereof)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
N- [ (1R) -2-hydroxy-1- (2-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Canton, calif.), JAB3312 (Canton, calif.), RLY1971 (Roche Co.), SAR442720 (Sainofein Co.), RMC4550 (Ind. ), RMC4630 (Ind., navirre), BBP398 (Navirre Co.), BR790 (Shanghai Qingyo pharmaceutical technology Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy, mars 601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nocheng, gmbH), HBI2376 (Huya), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng, datsukamura Co., ltd.) Medical Co., ltd.), X-37-SHP2 (X-37), )
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi), JAB3312 (Jiakeshi), RLY1971 (Roche), SAR442720 (Sanofei), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire), BR790 (Shanghai Qing Sei. Medical science Co., ltd.), SH3809 (Nanj Saint Co., ltd.), PF0724982 (Huy Corp.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co.), ICP189 (Nohon Ne Litsea), HBI2376 (Hu Asia), ETS001 (Shanghai Yi Bio-Ind.), S-AST X (Datsukamura and X37-37, SHP-37))
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, aprilsedge, or Erbuli, such as Aprilsedge)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salts, or a Raf inhibitor or its pharmaceutically acceptable salts (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or its pharmaceutically acceptable salts (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (3-hydroxy-1- (pyridin-2-yl) propyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a cMET inhibitor, or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- [ (1S) -3-hydroxy-1-methyl-propyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotosituba, aldarasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C,MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb) and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
N- [ (1S) -3-hydroxy-1-methyl-propyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolaci, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., compound C, sotolaci or adaglazeb)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, EGFR inhibitors, or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, aprilsedge, or Erbuli, e.g., aprilsedge)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirodelin))
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib, or a pharmaceutically acceptable salt thereof)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobicitinib, e.g., trametinib)
N- [ (1S) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a cMET inhibitor, or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor, or a pharmaceutically acceptable salt thereof
N- [ (1R) -3-hydroxy-1-methyl-propyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
N- [ (1R) -3-hydroxy-1-methyl-propyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additive manufacturing industry), JAB3312 (additive manufacturing industry), RLY1971 (roche company), SAR442720 (celecoxib company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolutionary pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai bright medical science limited), SH3809 (nansheng and company), PF0724982 ]The company of pyro), erat 601 (company of Erasca), RX-SHP2 (company of Redx pharmaceutical), ICP189 (company of nochon-jianhua), HBI2376 (company of huna), ETS001 (company of biological pharmacy of shanghai yi tuo), TAS-ASTX (company of roc and tsukamurelkava pharmaceutical corporation) and X-37-SHP2 (X-37), HBI2376 (company of hungaria),)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., compound C, sotolacib or adaglazeb)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, EGFR inhibitors, or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, aprilsedge, or Erbuli, e.g., aprilsedge)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobicitinib, e.g., tramatinib)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, ERK inhibitors, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinoid, or hdm201 (also known as sirodelin))
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib, or a pharmaceutically acceptable salt thereof)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobicitinib, e.g., trametinib)
N- [ (1R) -3-hydroxy-1-methyl-propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terpetinib, e.g., carbamazepine)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sainofei Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qinghai medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nardosta, santa Clara Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.) and X-37-SHP2 (X-37),)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotussilager, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotussilager or Aldaglazeb)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, naixib-bead mab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupanib, edalisis, copennisi, du Weili Sib, april, or Erburil plug, e.g., april)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodeline))
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib or a pharmaceutically acceptable salt thereof)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, wei Mo Feini or Darafenib)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
(S) -N- (4-aminobutan-2-yl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- [ 3-hydroxy-1- (2-pyridinyl) propyl group]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sotoracicb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, azkras G12C, NYU-12VC1, RMC6291 and compound C, such AS compound C, sotoracicb or adaglazeb) and a SHP2 inhibitor (e.g., a SHP2 inhibitor selected from the group consisting of TNO155, b3068 (acetate), b 2 (acetate), RLY1 (acetate), festivals (19750), pharmaceutical Ind (19750) Company), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), and SH3809 (Nanjing Saint Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Co., ltd.) RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Roc Co., ltd.), X-37-SHP2 (X-37), a, )
N- [ 3-hydroxy-1- (2-pyridinyl) propyl group]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37) )
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, edalrisis, copennisi, du Weili Sib, april, or Erbuli, e.g., april)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinone, or hdm201 (also known as sirodelin))
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobicitinib, e.g., tramatinib)
N- [ 3-hydroxy-1- (2-pyridinyl) propyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, enkefenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazetinib or tertiarypetide, e.g., carbamazetinib)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereofThe salt (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolacca, aldaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC, JAB-21822, AST-KRAS G12C, MRTX1257, AZKRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., compound C, sotolacca or Aldaglazeb) and SHP2 inhibitor (e.g., a SHP2 inhibitor selected from the group consisting of TNO155, JAB3312 (GmbH), RLY1971 (Rogowski), RL 442720 (Nofei), RMC4550 (Ind), BRC 4630), BRS (R.Ind), R.37, R.Ind.37, R.S. Shanghai Ind.37, R.37, R.Ind.Ind.37, R.Ind.37, R.Ind.Ind.37, R.Ind.Ind., )
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakeshi Co., ltd.), JAB3312 (Jiakeshi Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Safeofie Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing medical science Co., ltd.), SH3809 (Nagenie Co., ltd.), PF0724982 (Juy Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's Jian.), HBI2376 (Shanghai Cention), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), S-AST and SHP 37-37 (Sharpa) and SHP-37)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolaci, aldaglas, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaci or Aldaglas)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, apilimus, or Erburilius, e.g., apilimus)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semmetinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cilib, or a pharmaceutically acceptable salt thereof)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofeniil, wei Mo Feini, or Darafenib)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salt, or a Raf inhibitor or its pharmaceutically acceptable salt (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or its pharmaceutically acceptable salt (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(R) -N- (1- (azetidin-3-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a cMET inhibitor, or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -N- [1- (2-amino-3-pyridinyl) ethyl]-5- [4- (trifluoromethyl) phenyl ]]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
(R) -N- [1- (2-amino-3-pyridinyl) ethyl]-5- [4- (trifluoromethyl) benzeneBase group]Naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikeku), JAB3312 (jikeku), RLY1971 (roche), SAR442720 (sonofil), RMC4550 (revolutionary), RMC4630 (revolutionary), BBP398 (Navire), BR790 (liku medical science limited), SH3809 (nansheng and company), PF0724982 (fei company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, inc), HBI2376 (hunya organism), ETS001 (lozenges biological pharmaceutical company), TAS-apbook and large tsukamuse pharmaceutical company) and X-37-SHP2 (X-37))
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldaglas, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldaglas)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidaris, coupannix, du Weili Sib, april, or Erbuli, such as April)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib, or a pharmaceutically acceptable salt thereof)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, such as tramatinib)
(R) -N- [1- (2-amino-3-pyridinyl) ethyl ] -5- [4- (trifluoromethyl) phenyl ] naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g. carbamazepine or terpetinib, e.g. carbamazepine)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: soto-Laxib, aldag-Laxib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, soto-Laxib or Aldag-Laxib, and SHP2 inhibitor (e.g., SHP2 inhibitor selected from the group consisting of TNO155, JAB3068 (Gakesi), JAB3312 (Gakesi), RLY1971 (Roche Co.), SAR442720 (Nofei), C4550 (Ming Ind), RMC4630 (Navire), BBP398 (Navire), BR (Shanghai Ing), and YP 790 (SH 9, beijing technologies, inc.)) Saint Co., ltd.), PF0724982 (Congo Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya Biometrics), ETS001 (Shanghai Yituo Biometrics Co., ltd.), TAS-ASTX (Roc and tsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Conduca Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37))
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolacia, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldax)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidarios, domonan, du Weili Sibutine, april, or Erbutilide, e.g., april)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, e.g., trametinib)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, endoconcha, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- (pyridin-4-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g. carbamazepine or terpetinib, e.g. carbamazepine)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sotorax, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRT) X1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., compound C, sotoracicb, or adaglazeb) and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an inhibitor of SHP2 or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Conduca Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng) and X-37-SHP2 (X-37) )
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolacia, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldax)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethi, edalism, copennisi, du Weili Sib, april, or Erbuli plug, e.g., april)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semantenib, pimatinib, PD-0325901, and cobratinib, e.g., trametinib)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, such as LTT 462)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlein-3 a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinol or hdm201 (also known as sirodelin))
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei. Mu.m, naprafenib, endoconcha, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901, and cobratinib, such as trametinib)
N- (pyridin-2-ylmethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sainofei Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy Co.), ERAS601 (Erasca Co.), SHP2 (Redx Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Huya Co.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), and Ts, X-37-SHP2 (X-37), )
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jiku-shi-kola), JAB3312 (jiku-shi-kola), rliy 1971 (roc corporation), SAR442720 (sonofe corporation), RMC4550 (revolution pharmaceutical corporation), RMC4630 (revolution pharmaceutical corporation), BBP398 (Navire corporation), BR790 (Shanghai qing pharmaceutical technologies, inc.), SH3809 (nankingdom corporation), PF0724982 (parecox corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (norhon-ku-hua corporation), HBI2376 (hun-yabio), ETS001 (seay-ku-hua-shi-yu-hua) and taku-shi (hua-hua)Social Co., ltd.) and X-37-SHP2 (X-37), )
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, aldax, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or Aldax)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, spinetoram, nazatinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethi, edalisis, kupannix, du Weili Sibution, aprilsedge, or Erbutilisse, e.g., aprilsedge)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as siredelin))
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib, and abbe cinib, or a pharmaceutically acceptable salt thereof)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encolfenib, vitamin Mo Feini, or Darafenib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semtinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
N- (2-hydroxy-1- (pyridin-2-yl) ethyl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sainofei Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy Co.), ERAS601 (Erasca Co.), SHP2 (Redx Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Huya Co.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), and Ts, X-37-SHP2 (X-37), )
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakesi Co., ltd.), JAB3312 (Jiakesi Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Safenofei Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing, medical science Co., ltd.), SH3809 (Nanj Co., ltd.), PF0724982 (Hu Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nohon, santa.), HBI2376 (Hu Asia Co., ltd.), ETS001 (Shanghai Yi Bio-Biotech), S-AST (Dapeng and Datatsuk and X37-SHP 37) )
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, aprilsedge, or Erbuli, such as Aprilsedge)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salts, or a Raf inhibitor or its pharmaceutically acceptable salts (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or its pharmaceutically acceptable salts (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponitinib, e.g., carbamazepine)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of Sotolaci, adaglazest, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Che)m KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and compound C, such AS compound C, sotoracicb or adaglazeb, and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jiakesi Co., ltd.), JAB3312 (Jiakesi Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Safenofei Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing, medical science Co., ltd.), SH3809 (Nanj Co., ltd.), PF0724982 (Hu Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nohon, santa.), HBI2376 (Hu Asia Co., ltd.), ETS001 (Shanghai Yi Bio-Katsuk Co., ltd.), S-AST and SHP 37-37, SHX-37 & lt-) )
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolacib or adaglazeb)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazon, aidoris, coupannix, du Weili Sib, aprilsedge, or Erbuli, such as Aprilsedge)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salts, or a Raf inhibitor or its pharmaceutically acceptable salts (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or its pharmaceutically acceptable salts (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(R) -7-methoxy-N- (1- (pyridin-2-yl) ethyl) -5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Finnii, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a cMET inhibitor, or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or terponinib, e.g., carbamazepine)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sainofei Co.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (Buddy Co.), ERAS601 (Erasca Co.), SHP2 (Redx Co.), ICP189 (Nocheng Jianhua Co.), HBI2376 (Huya Co.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), and Ts, X-37-SHP2 (X-37), )
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or its medicinePharmaceutically acceptable salts and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (jikesi), JAB3312 (jikesi), rley 1971 (roche company), SAR442720 (sonofil company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolutionary pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai qing pharmaceutical technology limited), SH3809 (nanking & company), PF0724982 (trim company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norhenghua company), HBI2376 (hun subunit), ETS001 (heny bio-pharmaceutical company), TAS-ast (da and tsukamurella) and X-37-SHP2 (X-37)), TAS-ast (da and tsukamura pharmaceutical company))
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., KRAS G12C inhibitor selected from the group consisting of Sotolaccb, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, e.g., compound C, sotolaccb or adaglazeb)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and EGFR inhibitors or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxatinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethide, aidoris, coupannix, du Weili Sib, apicalide, or Erbutilide, e.g., aprilprist)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, bemetinib, semanteb, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as sirodelin))
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelib, or a pharmaceutically acceptable salt thereof)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide, or a pharmaceutically acceptable salt thereof, and a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthacenecarboxamide or its pharmaceutically acceptable salts, or a Raf inhibitor or its pharmaceutically acceptable salts (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and a MEK inhibitor or its pharmaceutically acceptable salts (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-0325901, and cobratinib, e.g., tramatinib)
(S) -N- (1-hydroxypropan-2-yl) -7-methoxy-5- (4- (trifluoromethyl) phenyl) -2-naphthamide or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof (e.g., carbamazetinib or topotinib, e.g., carbamazetinib) inhibitor or a pharmaceutically acceptable salt thereof
Any one of compound nos. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof of WO 2019/222431
Compound nos. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, and,164. 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co.), SAR442720 (Sanofei Co.), RMC4550 (Ind., revolution pharmaceutical Co.), RMC4630 (Ind., revolution pharmaceutical Co.), BBP398 (Navire Co.), BR790 (Shanghai Qingyu medical science Co., ltd.), SH3809 (Nanj St. And Co.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co.), SHP2 (Redx pharmaceutical Co.), ICP189 (Nohong Korea Co.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37), )
Any one of compound nos. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof, an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (additive manufacturing), JAB3312 (additive manufacturing), RLY1971 (roche company), SAR442720 (Sainofil Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yu Zhi medical science and technology Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Corp.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nucheng Jianhua Corp.), HBI2376 (Huya organism), ETS001 (Shanghai Yituo Biometrics Co., ltd.), TAS-ASTX (Roche and Tsukaki pharmaceutical Co., ltd.) and X-37-SHP2 (X-37),)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotolacia or adaglazeb
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof (e.g., any of erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dacatinib, toxib, tizantinib, LTT or dasatinib, such as LTT or erlotinib)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirises, idary, bannesi, du Weili sibirises, aperturens, or epleries, such as aperturens) of PI3K inhibitors or pharmaceutically acceptable salts thereof
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trimetinib, bemetinib, sematinib, PD-032501 and cobitinib, such as trimetinib)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, 08353, LTT462, or d-523, e.g., LTT-180, 182, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof
Any of compound numbers 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof, and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutin-3 a, idanolin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade mei or hdm201 (also known as siredelin)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203 or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of pamphleb, rebaudimide, and abbe. West) inhibitor or a pharmaceutically acceptable salt thereof
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof, a Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, napranafini, encouanib, vitamin Mo Feini, or darafinib)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encoufenib, vitamin Mo Feini, or dasfenib) and a MEK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramadol, betinib, mactinib, critinib, 032-5901, and triatinib)
Compound No. 2, 3, 5, 14, 15, 17, 22, 25, 26, 29, 41, 42, 44, 45, 47, 49, 51, 52, 54, 73, 75, 76, 77, 79-81, 83, 85-87, 96, 102, 108, 113-116, 120-124, 129, 130, 132, 135, 140, 146, 149, 152, 155, 158, 161, 162, 164, 166, 168, 171, 174, 178-180, 182, 184, 187, 190, 191, 197, 198, 201-203, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naplafenib, encoufenib, vitamin Mo Feini, or darafinib) and an ERK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-94, KO-947, vtx-772984, lttx-772984, MK, 353, 3214996, and/or bv 0953, or a pharmaceutically acceptable salt thereof)
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazetinib or topotinib, such as carbamazetinib), in WO 2019/113236
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30-33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotosib, adagransieb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC C, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS compound C, sotosia or adagransieb, and SHP2 inhibitors (e.g., SHP2 inhibitors selected from the group consisting of TNO155, JAB3068 (Gakesi), JAB3312 (Gakesi), RLY1971 (Roche), SAR442720 (Nafei), C4550 (R, ing), RMC4630 (R), BBP398 (Navire), BR (Shanghai), UK medicine), well (R790 (R9, R.Ind.), R.Chen.Chen.Chemicals), R.Ind., 3, R., ETS001 (Bio-pharmaceutical Co., ltd., hakka Yi Tuo Co., ltd.), TAS-ASTX (Roc, tukaki Co., ltd.), X-37-SHP2 (X-37), )
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., compound 1, 3, 7, 8, 1)0. 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, or a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jisco, JAB3312 (jikesika), RLY1971 (roche company), SAR442720 (sonofe company), RMC4550 (revolution pharmaceutical company), RMC4630 (revolution pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai green, pharmaceutical technologies limited), SH3809 (nanking sum company), PF0724982 (pyro company), erat 601 (Erasca company), RX-SHP2 (Redx pharmaceutical company), ICP189 (norheng, ku, HBI2376 (hun, da), ETS001 (yaku, da) and tsuki-tsuki, tsuki and tsu 37-37 and SHP-37) )
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 34, 36-43, 45, 46, 49-59 and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 34, 36, 37-43, 45, 46, 49-59 and 61) or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sotorax, adaglazeb, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, 3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC, b-21822, ja 12G 12-677, KRAS 6712, asa 6791, and asa 6712, and asa 6212, for example, KRAS 12C, amas 6791, and asa compound or a pharmaceutically acceptable salt thereof
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, cetuximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirinotecan, idary, copanicin, du Weili sibirica, apicalix, such as apicalix)
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, pimatinib, PD-032501, and cobicitinib, such as tramatinib)
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or D-523, e.g., LTT 462)
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, or hdm201 (also known as siredelin))
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59 and 61 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59 and 61) or a pharmaceutically acceptable salt thereof and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib and abbe cichlib) or a pharmaceutically acceptable salt thereof, of WO 2019/113236
Any one of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 (e.g., any one of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofenib, vitamin Mo Feini, or darifeanib) of WO 2019/113236
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30-33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naprafenib, ennafil, vitamin Mo Feini, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semitinib, PD-032501, and colpitinib, e.g., trametinib)
Any of compound numbers 1-8, 10, 11, 15, 21-23, 25, 27, 28, 30, 33, 34, 36-43, 45, 46, 49-59, and 61 of WO 2019/113236 (e.g., any of compounds 1, 3, 7, 8, 10, 11, 15, 25, 28, 30, 33, 34, 36, 37-43, 45, 46, 49-59, and 61) or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naprafenib, enkephalinib, vitamin Mo Feini, or darifenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK 353, LTT462, or d-523, e.g., LTT 462)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 of WO 2019/040380 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, or a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamatinib or terponinib, such as carbamatinib)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 of WO 2019/040380 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, or a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Any of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 of WO 2019/040380 (e.g., compound 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-1)49) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
Any one of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any one of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jisika), JAB3312 (jisika), RLY1971 (roche company), SAR442720 (innox), RMC4550 (RMC 4550), RMC4630 (r), BBP398 (navir), etc.)BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (Congo Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nucheng Jianhua Co., ltd.), HBI2376 (Shanghai Yao), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng and Datsukamu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37),)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 of WO 2019/040380 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotolacia or adaglazeb
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, of an EGFR inhibitor (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, zetimibeb, nalzatinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib
Any one of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any one of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, or a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., amg., AMG511, QAU421, bupirinotecan, airy, pannix, du Weili sibutriclib, apilimib, or erbilise, e.g., apicalico)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semanteb, PD-0325901 and cobicitinib, such as trametinib)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Any of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, of an MDM2 inhibitor (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade, or hdm201 (also known as risde)
Any one of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 (e.g., any one of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, or a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabosib, and Abelicinib
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 136, 137, 139-145, 147-149, 150 and 151 of WO 2019/040380 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, or a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, encofenib, vitamin Mo Feini or dabrafenib)
Compound No. 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 137, 139-145, 147-149, 150 and 151 (e.g., any of compounds 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encoofenib, vitamin Mo Feini, or darafinib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of, such as triminib, betinib, mestinib, mactinib, matritinib, 032501 and dasatinib, such as, etc.), WO 2019/040380
Any one of compound numbers 3, 14, 15, 17, 19-22, 26, 29, 40, 45, 48, 56-58, 64, 67, 72, 73, 79, 81, 82, 87, 88, 90, 92, 94, 95, 103, 105, 110-113, 116, 131, 137, 139-145, 147-149, 150 and 151 (e.g., any one of compound numbers 90, 92, 94, 95, 103, 110, 116, 131, 136, 137, 139-145, 147-149) or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encoofenib, vitamin Mo Feini, or darafinib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, tx-11e, SCH-772984, MK 0853, ltmk, 353, LTT 353, or d-523, e.g., bv-462, or d-523)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof, a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazetinib or topotinib, such as carbamazetinib)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, and MAPK pathway inhibitor, or a pharmaceutically acceptable salt thereof
Compound number 11 of WO 2018/204532,23. 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, and a KRAS G12/G13 inhibitor, or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Gakesi pharmaceutical Co., ltd.), JAB3312 (Gakesi pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Ind.), RMC4630 (Ind.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing St. Co., ltd.), PF0724982 (Hu Rayle Co., ltd.), ERAS601 (Erasca Co., ltd.), SHP2 (Redx pharmaceutical Co., ICP189 (Nohonglo Co., ltd.), HBI2376 (Huya Co., ltd.), ETS001 (Shanghai Yi Bio Co., ltd.), TAS-ASTX (Roc, tukaamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
Any one of compound numbers 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof, SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (jikusi pharmaceutical), JAB3312 (jikusi pharmaceutical), RLY1971 (roc corporation), SAR442720 (cinofil corporation), RMC4550 (enkephal pharmaceutical), RMC4630 (envoy pharmaceutical corporation), BBP398 (Navire corporation), BR790 (Shanghai-e technologies, limited corporation), SH 9 (south asia and corporation), 0724982 (rayleigh), era (era), er (r.s), r.s-37, r.37, r.v. biological use, r.37-37 (sha 37) and biological use (sha 37-37)
Compound numbers 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof, an inhibitor of KRAS G12/G13 or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of sottorx, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, j74699157, X-Chem KRAS, 3537982, BI1823911, AS KRAS G12C, SF KRAS 12C, RMC, b-21822, astm-KRAS 12G 7, KRAS 12G 12C inhibitor or a pharmaceutically acceptable salt thereof, e.g., a compound of jn-21822, astm-KRAS 12 g., KRAS 12C inhibitor or a pharmaceutically acceptable salt thereof, e.g., a compound of idazeylar 12, a compound of ida-koc, such AS may be used in the combination of one or more than one or more of these compounds
Compound numbers 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, an EGFR inhibitor, or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, spinetozumab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, a PI3K inhibitor, or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirises, idarubicin, kupannix, du Weili sibirises, aperilisis, e.g., aperilisis)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semitinib, PD-0325901 and cobratinib, such as trametinib)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, an ERK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT 462)
Compound nos. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also referred to as RG 7388), RG7112, AMG-232 (also referred to as KRT-232), APG-115, BI-907828, mi Lade maytans or hdm201 (also referred to as sridelin))
Compound number 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib and abbe cinib
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, and Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, napranafini, encofenib, vitamin Mo Feini, or darafenib)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264 or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxani, encouani, vitamin Mo Feini or darafani) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, pimatinib, PD-032501 and cobicitinib, such as tramatinib)
Compound No. 11, 23, 42, 60, 77, 98, 102, 105, 106, 108, 114, 116, 119, 123-125, 127, 129, 131, 139, 151, 152, 169, 173, 175, 181, 186-188, 191-195, 201, 204, 210, 212, 218, 238-244, 246, 254-256, 260, 263 and 264, or a pharmaceutically acceptable salt thereof, and Raf inhibitor, or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naprafenib, encolfenib, vitamin Mo Feini, or darifenib), and ERK inhibitor, or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or ltd-523, e.g., LTT bvt 462)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, e.g., carbamazepine)
Any one of compound numbers 1-58 of WO 2020/051099 (preferably any one of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Any one of compound numbers 1-58 of WO 2020/051099 (preferably any one of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of: sotosib, adagransieb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS compound C, sotosib or adagransieb, and SHP2 inhibitors (e.g., SHP2 inhibitors selected from the group consisting of TNO155, JAB3068 (Gakesi pharmaceutical), JAB3312 (Gakesi), RLY1971 (Roche), SAR442720 (Sanofei), C4550 (Ming, ming., ming, ing., gmbH) and SHP2 inhibitors ) BBP398 (Navire Corp.), BR790 (Shanghai Qing Yu medical science Co., ltd.), SH3809 (Nanjing Saint He Corp.), PF0724982 (pyro Corp.), ERAS601 (Erasca Corp.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nucheng Jianhua Corp.), HBI2376 (Shangya Corp.), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng and Datsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compound 54, 55, 56A, 56B, 57A, 57B and 58, preferably any of compound 58) or a pharmaceutically acceptable salt thereof and a SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g. TNO155, JAB3068 (jikesi pharmaceutical industry), JAB3312 (jikesi pharmaceutical industry), RLY1971 (rogows), 442720 (sainfie company), RMC4550 (revolutionary pharmaceutical company), RMC4630 (revolutionary pharmaceutical company), SAR 398 (Navire company), BR790 (Shanghai green medical science, SH3809 (nanjing & company), PF0724982 (part company), erat 601 (Sharca company), RX-SHP2 (Redx pharmaceutical company), ICP (part), noni 2376 (lozenges), et001 (Shanghai) s001 (yinghai biosystems), tsche-37-X (sham), tsujoba 37-X (sham) and majoba-37-X (sham) )
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g. a KRAS G12C inhibitor selected from the group consisting of sotoracicb, adaxazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and compound C, e.g. compound C, sotoracicb or adaxazeb)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixituzumab, nazatinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirimate, erila, copan, du Weili sibutril, apicalicheat or ependymal, e.g., apicalicheat)
Any one of compound numbers 1-58 of WO 2020/051099 (preferably any one of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semetinib, pimatinib, PD-0325901 and cobratinib, e.g., trametinib)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine or hdm201 (also known as sireide))
Any one of compound numbers 1-58 of WO 2020/051099 (preferably any one of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of palbociclib, rebabociclib and abbe cilib or a pharmaceutically acceptable salt thereof)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxen, enkephalin, vitamin Mo Feini or dabrafenib)
Any one of compound numbers 1-58 of WO 2020/051099 (preferably any one of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei ni, naproxani, enkephalin, vitamin Mo Feini or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of tramatinib, bemetinib, sematinib, pimatinib, PD-032501 and cobicitinib, such as tramatinib)
Any of compound numbers 1-58 of WO 2020/051099 (preferably any of compounds 54, 55, 56A, 56B, 57A, 57B and 58, preferably compound 58) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, england Fenib, vitamin Mo Feini or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., carbamazepine or topotinib, such as carbamazepine)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343, I-352, e.g., I-186 or I-12 of I-170) or a pharmaceutically acceptable salt thereof, MAsalt thereof
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of I-45, I-170, such as I-186, for example)1 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, or a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Calif.), JAB3312 (Calif.), RLY1971 (Roche Co., ltd.), SAR442720 (Sainofein Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navirre Co., ltd.), BR790 (Shanghai Qing medical science and technology Co., ltd.), SH3809 (Najing holy & Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nocheng's health, ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yi Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.), X-37-SHP2 (X-37) )
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Gakex pharmaceutical Co., ltd.), JAB3312 (Gakex pharmaceutical Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Saenofil Co., ltd.), RMC4550 (Innovative pharmaceutical Co., ltd.), RMC4630 (Innovative pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qing Yuan medical science Co., ltd.), SH3809 (Nanjing Sheng Co., ltd.), PF0724982 (Huy Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nuas Cheng Jianhua Co., ltd.), HBI2376 (Shanghai Asia), ETS001 (Shanghai Yi Tuo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng and Dai Katsu pharmaceutical Co., ltd.) and X-37-SHP2 (X-37), )
Any one of the compounds selected from the group consisting of isomer 2 of tables 1, 2 and I-12 of WO 2020/243323 (e.g., any one of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, I-208, 211, 220, 222, 231, I-334, I-341, I-343, I-352, e.g., I-186, I-12) or a pharmaceutically acceptable salt thereof, e.g., KRAS 12, and a pharmaceutically acceptable salt thereof selected from the group consisting of KRAS 12 or a pharmaceutically acceptable salt thereof (e.g., a pharmaceutically acceptable salt of KRAS 12 or a pharmaceutically acceptable salt thereof; sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotolacia or adaglazeb
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, or an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactinib, naixib, nazatinib, LTT462, or vandetanib, such as LTT462 or erlotinib)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bunazomethie, edalrisil, copan, du Weili sibutramine, april, or Erbuli, such as April)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of: trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, or an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansinone, or hdm201 (also known as sirolimus)
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4/6 inhibitor selected from the group consisting of: palbociclib, rebamiphene and abbe's west ib
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini, or Darafenib)
Any one of the compounds selected from the group consisting of isomer 2 of table 1, table 2 and I-12 of WO 2020/243323 (e.g. any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, isomer 1 of I-170, isomer 2 of I-175, isomer 2 of I-177, isomer 2 of I-180, isomer 1 of I-182, isomer 1 of I-186, isomer 1 of I-189, 208, 211, 220, 222, 231, I-334, any one of isomer 1 of I-334, isomer 1 of I-341, or isomer 2 of I-352, e.g. isomer 1 of I-186 or isomer 2 of I-170) or a pharmaceutically acceptable salt thereof, e.g. a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable salt thereof, e.g. a prandial inhibitor, or a pharmaceutically acceptable salt thereof, such as a prandial inhibitor, 35 or a pharmaceutically acceptable salt thereof, of the group of the drugs selected from the group consisting of MEK 35, 35 or a pharmaceutically acceptable salt thereof; trametinib, bemetinib, semetinib, pimarictinib, PD-0325901 and cobitinib, e.g. trametinib
Any one of the compounds selected from the group consisting of isomer 2 of Table 1, table 2 and I-12 of WO 2020/243323 (e.g., any one of isomer 1 of I-27, I-30, I-31, I-35, I-36, I-40, I-44, I-45, I-64, I-69, I-70, I-71, I-77, I-170, I-175, I-177, I-180, I-182, I-186, I-188, I-189, 208, 211, 220, 222, 231, I-334, I-341, I-343 or I-352 of isomer 1, I-35, for example, isomer 1 of I-186 or isomer 2 of I-12) or a pharmaceutically acceptable salt thereof, a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei Ni, naprafenib, endoconfenib, vitamin Mo Feini, or Darafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., uliptinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, such as LTT 462)
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g. any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g. carbamazetinib or topotinib, e.g. carbamazetinib)
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g.any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and an MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof
Any one of the compounds selected from table 1 or table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84, and I-85) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacib, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, such AS Compound C, sotolacib, or adaglazeb), and an SHP2 inhibitor (e.g., an SHP2 inhibitor selected from the group consisting of: TNO155, JAB3068 (Gakeshi Co., ltd.), JAB3312 (Gakeshi Co., ltd.), RLY1971 (Roche Co., ltd.), SAR442720 (Sanofei Co., ltd.), RMC4550 (revolution pharmaceutical Co., ltd.), RMC4630 (revolution pharmaceutical Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai Qinghua pharmaceutical technology Co., ltd.), SH3809 (Nanjing san Co., ltd.), PF0724982 (PY Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical Co., ltd.), ICP189 (Nochengjianhua Co., ltd.), HBI2376 (Huya organism), ETS001 (Shanghai Yituo Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng, datsukamu pharmaceutical Co., ltd.), X-37-SHP2 (X-37), )
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g.any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g.TNO 155,JAB3068 (Gakesi pharmaceutical industry), JAB3312 (Gakesi pharmaceutical industry), RLY1971 (Roche company), SAR442720 (Sanofei company), RMC4550 (revolution pharmaceutical company), RMC4630 (revolution pharmaceutical company), BBP398 (Navire company), BR790 (Shanghai Qinghai medical science and technology Co., ltd.), SH3809 (Nanjing Saint Co., ltd.), PF0724982 (pyro Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx pharmaceutical company), ICP189 (Nocheng Jianhua Co., ltd.), HBI2376 (Shanghai Yi Tu Yao Co., ltd.), ETS001 (Shanghai Yi Tu Bio-pharmaceutical Co., ltd.), TAS-ASTX (Dapeng Co., ltd.) and X-37-SHP2 (X-37),)
Any one of the compounds selected from table 1 or table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84, and I-85) or a pharmaceutically acceptable salt thereof and a KRAS G12/G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C inhibitor selected from the group consisting of: sotolacia, adaglazeb, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, such AS Compound C, sotolacia or adaglazeb
Any one of the compounds selected from table 1 or table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84, and I-85) or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, oxtinib, lenatinib, gefitinib, cetuximab, panitumumab, dactinib, rituximab, nazatinib, LTT462, or vandetanib, e.g., LTT462 or erlotinib)
Any one of the compounds selected from Table 1 or Table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, bupirinotecan, airaris, copennisil, du Weili sibirica, apicalide or epcalix, e.g., apicalicheat)
Any one of the compounds selected from Table 1 or Table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, semitinib, pimelitinib, PD-0325901 and cobicitinib, e.g., trametinib)
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulittinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT 462)
Any one of the compounds selected from Table 1 or Table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idanulin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine or hdm 201) of WO 2020/243315
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g.I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and for a CDK4/6 inhibitor or a pharmaceutically acceptable salt thereof (e.g.a CDK4/6 inhibitor selected from the group consisting of Pabosib, rabostinib and Abelitinib or a pharmaceutically acceptable salt thereof)
WO 2020/243315 for any one of the compounds selected from Table 1 or Table 2 (e.g. any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84 and I-85) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g. Bei Fafei Ni, naprafenib, encofenib, vitamin Mo Feini or Darafenib)
Any one of the compounds selected from table 1 or table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84, and I-85) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naproxani, encofenib, vitamin Mo Feini, or dabrafani) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, bemetinib, sematinib, PD-032501, and bicatinib, e.g., trametinib)
Any one of the compounds selected from Table 1 or Table 2 (e.g., any one of I-27, I-30, I-31, I-32, I-33, I-36, I-37, I-38, I-51, I-54, I-59, I-65, I-67, I-68, I-74, I-75, I-80, I-81, I-84, and I-85) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., bei Fafei, naprafenib, encofinib, vitamin Mo Feini, or Darafinib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., preferably iritinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, 462, LY3214996, MK 353, LTT462, or D-523, e.g., LTT BV 08T)
In an embodiment, the TEAD inhibitor is selected from any one of the compounds disclosed in Table 1 of WO 2020/243423. In an embodiment, the TEAD inhibitor is selected from any one of the examples disclosed in Table 1 of WO 2020/243415, e.g/>
Also disclosed herein are any of the combinations exemplified above for use in cancer treatment.
Also disclosed herein is a first named combination partner of any of the combinations exemplified above for use in cancer therapy, wherein the therapy further comprises administration of a second named combination partner (and a third named combination partner when present) (e.g., when combined as compound B and trametinib, disclosed is compound B for use in cancer therapy, wherein the therapy further comprises administration of trametinib).
Also disclosed herein is a second named combination partner of any of the combinations exemplified above for use in cancer therapy, wherein the therapy further comprises administration of the first named combination partner (and a third named combination partner when present) (e.g., when combined as compound B and trimetinib, disclosed is trimetinib for use in cancer therapy, wherein the therapy further comprises administration of compound B).
Also disclosed herein is a third named combination partner of any of the above-exemplified triple combinations for use in cancer treatment, wherein the treatment further comprises administration of the first named and second named combination partners.
Also disclosed herein is a method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a combination of a first named combination partner and a second named combination partner (and a third named combination partner when present).
As used herein, the term "cMET inhibitor" includes, but is not limited to, the group consisting of: tivanitinib, furitinib, cabozitinib, crizotinib, carbamazepine, AMG337, wo Liti, BMS777607, geestinib, terpetinib, onatuzumab, rituximab, fepratuzumab, ematuzumab, and any pharmaceutically acceptable salts thereof. In embodiments, the cMET inhibitor is selected from the group consisting of: cabozantinib, crizotinib, carbamatinib, and any pharmaceutically acceptable salts thereof. In embodiments, the cMET inhibitor is carbamazepine, or a pharmaceutically acceptable salt thereof. The carbamazepine has the formula:
And is also known as 2-fluoro-N-methyl-4- [ 7-quinolin-6-yl-methyl) -imidazo [1,2-b ] [1,2,4] triazin-2-yl ] benzamide or "INC280". The carbamazepine can be synthesized according to, for example, the methods disclosed in U.S. patent nos. 7,767,675 and 8,420,645, which are incorporated herein by reference in their entirety. U.S. patent No. 8,420,645 also discloses salts and solvated (e.g., hydrated) forms of carbamazepine that may be used in the combinations of the present invention. For example, in some embodiments, the carbamazepine is dihydrochloride. In some embodiments, the carbamazepine is the monohydrate of the dihydrochloride (i.e., 2-fluoro-N-methyl-4- [7- (quinolin-6-ylmethyl) imidazo [1,2-b ] [1,2,4] triazin-2-yl ] benzamide-hydrogen chloride-water (1/2/1)).
As used herein, the term "KRAS G12/G13 inhibitor" includes, but is not limited to, KRAS G12C inhibitors. Preferably, the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor. The term KRAS G12C inhibitor includes, but is not limited to, the group consisting of: 1- {6- [ (4M) -4- (5-chloro-6-methyl-1H-indazol-4-yl) -5-methyl-3- (1-methyl-1H-indazol-5-yl) -1H-pyrazol-1-yl ] -2-azaspiro [3.3] heptan-2-yl } prop-2-en-1-one (Compound C), sotoraciclovir (Megaku's Ann), adaglazeb (Mirati), D-1553 (beneficial organism), BI1701963 (Boringer's company), GDC6036 (Roche company), JNJ74699157 (Qiangsheng company), X-Chem KRAS (X-Chem company), LY3537982 (Gift's company), BI1823911 (Boringer's company), AS KRAS 12C (sub-flourishing pharmaceutical company), SF KRAS G12C (Fei's corporation), RMC032 (pharmaceutical company), AZB-21822 (Jia's Angora), AST-KR 12G 12 (Mirax), KR 12C (RY 12C), KR 12 (Yoghuru's) or a pharmaceutically acceptable salt thereof, and pharmaceutical salt thereof (Yoghurt 1). In embodiments, the KRAS G12C inhibitor is selected from the group consisting of: compound C, sotoracicb and adaglazeb. In embodiments, the KRAS G12 inhibitor is compound C. Compound C is also known as "JDQ443" or "NVP-JDQ443" and is described in example 1a of published PCT application WO 2021/124222, month 6, 24 of 2021.
As used herein, the term "KRAS G12/G13 inhibitor" also includes, but is not limited to, compounds selected from the group consisting of: 1- (4- (6-chloro-8-fluoro-7- (3-hydroxy-5-vinylphenyl) quinazolin-4-yl) piperazin-1-yl) prop-2-en-1-one-, -methane (1/2); (S) -1- (4- (6-chloro-8-fluoro-7- (2-fluoro-6-hydroxyphenyl) quinazolin-4-yl) piperazin-1-yl) prop-2-en-1-one; and 2- ((S) -1-propenoyl-4- (2- (((S) -1-methylpyrrolidin-2-yl) methoxy) -7- (naphthalen-1-yl) -5,6,7, 8-tetrahydropyrido [3,4-d ] pyrimidin-4-yl) piperazin-2-yl) acetonitrile, any of the compounds detailed in the following documents: WO 2013/155223, WO 2014/143659, WO 2014/152588, WO 2014/160200, WO 2015/054572, WO 2016/044772, WO 2016/049524, WO 2016164675, WO 2016168540, WO2017/058805, WO 2017015562, WO 2017058728, WO 2017058768, WO 2017058792, WO 2017058805, WO 2017058807, WO 2017058902, WO 2017058915, WO 2017087528, WO 2017100546, WO 2017/20161, WO 2018/064510, WO 2018/068017, WO 2018/119183, WO 2018/217651, WO 2018/140512, WO 2018/14059, WO 2018/140600, WO 2018/143315, WO 2018/206539, WO 2018/218069, WO 2018/218070, WO 2018/218071, WO 2019/0519/05124, WO 2018/219551; WO 2019/110751, WO 2019/141250, WO 2019/150305, WO 2019/155399, WO 2019/213516, WO 2019/213526, WO 2019/215203, WO 2019/21737 and WO 2019/217691, WO 2019/232419, WO 2020/028706, WO 2020/047192, EP 3628664, WO 2020081282, WO 2020085504, WO 2020/085493, WO 2020/097537, WO 2020/106640, WO 2020/113071, WO 2020/146613, WO 2020/156285, WO 2020/181110, WO 2020/178282, WO 2020/216190, WO 2020/236940, WO 2020/23592, WO 2020/238791, WO 2020/239077, WO 2020/239123, WO 2020/259513, WO 2020/259573, WO 2020/259432, WO2021/000885, WO 2021/0239154, WO 2021/027943 WO 2021/027911, CN 112390796, WO 2021/037018, CN 112430234, CN 112442029, WO 2021/043322, WO 2021/055728.
As used herein, the term "SHP2 inhibitor" includes, but is not limited to, compounds described in the following documents: WO 2015/107493, WO 2015/107494, WO 2015/107495, WO 2016/203406, WO 2016/203404, WO 2016/203405, WO 2017/216706, WO 2017/156397, WO 2020/063260, WO 2018/172984, WO 2017/211303, WO 21/061706, WO 2019/183367, WO 2019/183364, WO 2019/165073, WO 2019/067843, WO 2018/218133, WO 2018/081091, WO 2018/057884, WO 2020/247643, WO 2020/076723, WO 2019/199792, WO 2019/118909, WO 2019/075265, WO 2019/051084, WO 2018/136264, WO 2018/013597, WO 2020/033828, WO 2019/318, WO 2019/158019, WO 2020845/08145, WO 2019/0845/2020; WO 21/018287, WO 2020/094018, WO 2021/033153, WO 2020/022323, WO 2020/177653, WO 2021/073439, WO 2020/156243, WO 2020/156242, WO 2021/147879, WO 2020/061101, WO 2019/233810, WO 2021/110796, WO 2020/073949, WO 2020/061103, WO 2021/115286, WO 2021/119525, WO 2021/121397, WO 2021/143680, WO 2021/143823, WO 2021/11480, WO 2020/249079, WO 2020/033286, WO 2021/061515, WO 2019/182960, WO 2020/094104, WO 2020/210384, WO 2020/181283, WO 2021/043077, WO 2021/028362, WO 2020/259679, WO 2020/108590 and WO 2019/469 TNO155 JAB3068 (jisco pharmaceutical industry), JAB3312 (jisco pharmaceutical industry), rley 1971 (roc corporation), SAR442720 (sonofi corporation), RMC4550 (revolutionary pharmaceutical corporation), RMC4630 (revolutionary pharmaceutical corporation), BBP398 (Navire corporation), BR790 (Shanghai qing medical science and technology limited), SH3809 (south-Beijing holy & corporation), PF0724982 (schiry corporation), erat 601 (Erasca corporation), RX-SHP2 (Redx pharmaceutical corporation), ICP189 (norhenk healthcare corporation), HBI2376 (hunya corporation), ETS001 (shanghai yi biopharmaceutical corporation), TAS-ASTX (large peng corporation) and X-37-SHP2 (X-37). In embodiments, the SHP2 inhibitor is selected from the group consisting of: TNO155, JAB3068 (Kochia pharmaceutical Co.), JAB3312 (Kochia pharmaceutical Co.), and RMC4630 (Sesamara pharmaceutical Co.). In an embodiment, the SHP2 inhibitor is TNO155.
As used herein, the term "EGFR inhibitor" includes, but is not limited to, the group consisting of:
erlotinib, oxcetinib, lenatinib, gefitinib, cetuximab, panitumumab, lapatinib, dactyltinib, cetuximab, nazatinib, LTT462, and vandetanib. In embodiments, the EGFR inhibitor is selected from the group consisting of: cetuximab, panitumumab, erlotinib, gefitinib, oxcetinib, nazatinib, and LTT462. In embodiments, the EGFR inhibitor is LTT462 or erlotinib.
As used herein, the term "PI3K inhibitor" includes, but is not limited to, the group consisting of: AMG511, bupanib, aidorsi, copennisi, du Weili Sib, april, QAU421 ((S) -N) 1 - (5- (2- (tert-butyl) pyrimidin-4-yl) -4-methylthiazol-2-yl) pyrrolidine-1, 2-dicarboxamide-closed ring analogue of apicalide) and erbumine. In embodiments, the PI3K inhibitor is apicalist or QAU 421).
As used herein, the term "ERK inhibitor" includes, but is not limited to, the group consisting of: yorittinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523. In embodiments, the ERK inhibitor is selected from the group consisting of: ulitinib, LTT462, gdc=0994, KO-947, vtx-11e, SCH-722894, MK2853 and LY3214996. In embodiments, the ERK inhibitor is LTT462 or ulitinib. In embodiments, the ERK inhibitor is LTT462.
As used herein, the term "MEK inhibitor" includes, but is not limited to, the group consisting of: trametinib, bemetinib, semetinib, pimetinib, PD-0325901 and cobratinib. In an embodiment, the MEK inhibitor is trametinib.
As used herein, the term "CDK4/6 inhibitor" includes, but is not limited to, rebamactinib, pamphleb, and abbe. In embodiments, the CDK4/6 inhibitor is rebaudinib (also known as LEE 011).
As used herein, the term "Raf inhibitor" includes, but is not limited to Bei Fafei ni, naproxen, vitamin Mo Feini, encofenib, and dabrafen. In embodiments, the Raf inhibitor is naprafenib or dabrafenib.
As used herein, the term "Mdm2 inhibitor" refers to any compound that inhibits HDM2/p53 (Mdm 2/p 53) interaction association. HDM2 (a human homolog of murine double minute 2) is a negative regulator of p 53. The Mdm2 inhibitors may be used in pharmaceutical compositions for human or veterinary use, wherein inhibition of Mdm2/p53 association is indicated, for example, in the treatment of tumors and/or cancerous cell growth. As used herein, the term "Mdm2 inhibitor" includes nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine, and hdm201 (also known as sirodelin). In embodiments, the Mdm2 inhibitor is selected from AMG-232 and HDM201. In an embodiment, the Mdm2 inhibitor is HDM201.
As used herein, the term "MAPK pathway" or "MAP kinase pathway" (also known as the MPK/ERK pathway and the Ras-Raf-MEK-ERK pathway) is well known to those skilled in the art and refers to a protein chain that communicates signals from a cell receptor to DNA present in the nucleus of a cell. The "MAP kinase pathway" includes, but is not limited to EGFR, GRB2, SOS, RAS, RAF and MEK.
As used herein, the term "C 1 -C 6 Alkyl "refers to a straight or branched hydrocarbon chain group consisting of only carbon and hydrogen atoms, free of unsaturation, having one to six carbon atoms, and attached to the remainder of the molecule by a single bond. The term "C 1 -C 3 Alkyl "and" C 1 -C 4 Alkyl "should be construed accordingly. C (C) 1 -C 6 Examples of alkyl groups include, but are not limited to: methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butylN-pentyl, 1-dimethylethyl (tert-butyl) and hexyl.
In general, unless otherwise indicated herein or clearly contradicted by context, for substituents comprising two or more subunits, the last-mentioned group is a group attachment point, e.g. "alkylaryl" means a monovalent group of the formula alkyl-aryl-, and "arylalkyl" means a monovalent group of the formula aryl-alkyl-.
As used herein, the term "hydroxy C 1 -C 4 Alkyl "means-R a -OH, wherein R a Is C as defined above 1 -C 4 An alkyl group. Hydroxy C 1 -C 4 Examples of alkyl groups include, but are not limited to: hydroxy-methyl, 2-hydroxy-ethyl, 2-hydroxy-propyl and 3-hydroxy-propyl.
As used herein, the term "hydroxy C 1 -C 3 Alkyl "means-R a -OH, wherein R a Is C as defined above 1 -C 3 An alkyl group. Hydroxy C 1 -C 3 Examples of alkyl groups include, but are not limited to: hydroxy-methyl, 2-hydroxy-ethyl, 2-hydroxy-propyl and 3-hydroxy-propyl.
As used herein, the term "C 3 -C 6 Cycloalkyl "refers to a saturated monocyclic hydrocarbon group of 3 to 6 carbon atoms. C (C) 3 -C 6 Examples of cycloalkyl groups include: cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
As used herein, the term "C 1 -C 6 Alkoxy "means-OR a Wherein R is a group of a Is C as generally defined above 1 -C 6 An alkyl group. The term "C 1 -C 3 Alkoxy "and" C 1 -C 4 Alkoxy "should be construed accordingly. C (C) 1 -C 6 Examples of alkoxy groups include, but are not limited to: methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, and hexoxy.
As used herein, the term "C 1 -C 3 -alkoxy-C 1 -C 3 Alkyl "means C as defined above 1 -C 3 -an alkyl group, wherein C 1 -C 3 One hydrogen atom of the alkyl radical being replaced by C 1 -C 3 -alkoxy substitution.
"halogen" or "halo" refers to fluorine, chlorine, bromine or iodine. Preferably, the halo is fluoro, chloro or bromo. More preferably, the halo is fluoro or chloro.
The term "oxo" refers to the group = O.
The term "sulfonyl" refers to the group-S (=o) 2 -。
The term "amino" refers to the group-NH 2 。
The term "NHR 1b "means the radical-N (H) R 1b . Similarly, e.g. "NR 5a R 5b The term "refers to the group-N (R 5a )R 5b 。
The term "halogen C", as used herein 1 -C 3 Alkyl "or" halo C 1 -C 3 Alkyl "means C as defined above substituted with one or more halo groups as defined above 1 -C 3 An alkyl group. Halogen C 1 -C 3 Examples of alkyl groups include, but are not limited to: trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 1-difluoroethyl, 2-trifluoroethyl, 2-fluoropropyl, 3-difluoropropyl and 1-fluoromethyl-2-fluoroethyl.
The term "halo C", as used herein 1 -C 6 Alkoxy "means C as defined above 1 -C 6 Alkoxy group, wherein C 1 -C 6 At least one hydrogen atom in the alkoxy group is replaced by a halo group as defined above. The term "halogenated C 1 -C 3 Alkoxy "should be construed accordingly. Halogenated C 1 -C 6 Examples of alkoxy groups include, but are not limited to: trifluoromethoxy, difluoromethoxy, trifluoroethoxy, 2-fluoropropoxy, 3-difluoropropoxy.
As used herein, the term "hydroxy C 1 -C 6 Alkoxy "means C as defined above 1 -C 6 Alkoxy group, wherein C 1 -C 6 In alkoxy groupsAt least one hydrogen atom is replaced by OH. The term "hydroxy C 1 -C 3 Alkoxy groups should be construed accordingly. Hydroxy C 1 -C 6 Examples of alkoxy groups include, but are not limited to, hydroxymethyl, hydroxyethoxy, 2-hydroxypropoxy.
As used herein, the term "C 1 -C 3 Alkoxy C 1 -C 3 Alkoxy "means C as defined above 1 -C 3 Alkoxy group, wherein C 1 -C 3 One hydrogen atom of the alkoxy group being replaced by-O-C 1 -C 3 Alkyl substitution. C (C) 1 -C 3 Alkoxy C 1 -C 3 Examples of alkoxy groups include, but are not limited to: 2-methoxyethoxy.
The term "halo C", as used herein 1 -C 3 alkoxy-C 1 -C 3 Alkyl "means C as defined above 1 -C 3 An alkyl group, wherein C 1 -C 3 Halogenated C wherein one hydrogen atom of the alkyl group is as defined above 1 -C 3 Alkoxy substitution. Halogenated C 1 -C 3 alkoxy-C 1 -C 3 Examples of alkyl groups include, but are not limited to: (difluoromethoxy) methyl (i.e. CHF 2 -O-CH 2 -)。
The term "C (O) NR, as used herein 1c R 1d "means-R a1 -N(R a2 ) 2 Wherein R is a group of a1 Is a carbonyl group, and each R a2 R is as defined herein, which may be the same or different 1c Or R is 1d A group.
As used herein, the term "C (O) di (C 1 -C 3 Alkyl) amino "means a compound of formula-R a1 -N(R a2 ) 2 Wherein R is a group of a1 Is a carbonyl group, and each R a2 Is C as defined herein, which may be the same or different 1 -C 3 An alkyl group.
The term "C (O) C", as used herein 1 -C 3 Alkyl "means-R a1 -C 1 -C 3 A radical of an alkyl group, wherein R a1 Is carbonyl groupA group, and C 1 -C 3 Alkyl is as defined above.
As used herein, the term "C (O) NHR 6a "means-R a1 -N(H)-R 6a Wherein R is a group of a1 Is a carbonyl group, and R 6a As defined herein.
The term "S-halo C", as used herein 1 -C 3 Alkyl "means-S-halo C 1 -C 3 Alkyl group, wherein halo is C 1 -C 3 Alkyl is as defined above.
As used herein, the term "C (O) OC 1 -C 3 Alkyl "means-R a1 -O-C 1 -C 3 A radical of an alkyl group, wherein R a1 Is a carbonyl group, and C 1 -C 3 Alkyl is as defined above.
As used herein, the term "SO 2 C 1 -C 3 Alkyl "means-S (=o) 2 -R a2 Wherein R is a group of a2 Is C as defined above 1 -C 3 An alkyl group.
As used herein, the term "C 1 -C 3 Alkylene "refers to a straight or branched hydrocarbon chain divalent group consisting of only carbon and hydrogen atoms, free of unsaturation, and having one to three carbon atoms. At Q (or Q) 1 ) Is C-substituted with 4-, 5-or 6-membered saturated heterocyclic ring 1 -C 3 In embodiments in which alkylene is substituted to form a bridge between the two ring atoms of the saturated heterocyclic ring, thereby forming a bridged bicyclic structure, the C 1 -C 3 The alkylene group is preferably propylene (-CH) 2 -CH 2 -CH 2 (-), ethylene (-CH) 2 -CH 2 (-) or methylene (-CH) 2 -)。
The term "(CH) 2 ) 0-2 R 1a "means- (CH) 2 ) 0-2 R 1a The radicals of (2), i.e. the radicals R 1a Attached to the remainder of the molecule via a bond, methylene linker or ethylene linker.
The term "(CH) 2 ) 0-1 C (O) di (C) 1 -C 3 Alkyl) amino "means- (CH) 2 ) 0-1 -R a3 And R is a group of a3 Is C (O) di (C) as defined above 1 -C 3 Alkyl) amino groups.
Term (CH) 2 ) 0-1 C(O)NR 1c R 1d Refers to- (CH) 2 ) 0-1 C(O)NR 1c R 1d Is a group of (2).
As used herein, the term "5 or 6 membered saturated heterocyclic ring containing at least one heteroatom selected from N and O" refers to a single ring and includes, but is not limited to: piperazinyl, piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, dioxanyl, and morpholinyl. Preferably, the term includes piperidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl and morpholinyl. The terms "5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O" and "6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O" should be construed accordingly.
As used herein, the term "comprises a member selected from N, O, S, -S (=o) and-S (=o) 2 A 4-, 5-, or 6-membered saturated heterocyclic ring "of at least one heteroatom or heteroatom group means a single ring and includes, but is not limited to: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl, or S, S-dioxothiomorpholinyl. For the avoidance of doubt, in certain embodiments where N is present at the α position of the atom that binds Q to the remainder of the molecule, this may be represented by the formula:
/>
as used herein, the term "5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, or S, preferably selected from N or S" refers to a monocyclic aromatic ring. Examples of such terms include, but are not limited to: oxazolyl, isoxazolyl, pyrimidinyl, pyridazinyl, tetrazolyl, pyrazinyl, triazolyl, imidazolyl, pyrazolyl, pyridinyl, and thiazolyl.
As used herein, the term "5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, and S" refers to an aromatic monocyclic ring and includes, but is not limited to: pyrimidinyl, pyridazinyl, tetrazolyl, pyrazinyl, triazolyl, imidazolyl, pyrazolyl, pyridinyl, oxazolyl, and thiazolyl. The attachment point to the imidazolyl ring is preferably attached to the nitrogen atom of the imidazolyl ring.
As used herein, the term "5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N and S" refers to a monocyclic aromatic ring and includes, but is not limited to: pyrimidinyl, pyridazinyl, tetrazolyl, pyrazinyl, triazolyl, imidazolyl, pyrazolyl, pyridinyl, and thiazolyl.
As used herein, the term "6-membered aromatic heterocycle containing at least one N heteroatom" refers to a monocyclic aromatic ring and includes, but is not limited to: pyrimidinyl, pyridazinyl, pyrazinyl and pyridinyl.
As used herein, the term "5-membered aromatic heterocycle containing at least one N heteroatom" (where N may also be NH) refers to a monocyclic aromatic ring and includes, but is not limited to: tetrazolyl, triazolyl, imidazolyl, and pyrazolyl.
As used herein, the term "5-or 6-membered aromatic heterocycle containing at least one N heteroatom" refers to a monocyclic aromatic ring and includes, but is not limited to: pyrimidinyl, pyridazinyl, tetrazolyl, pyrazinyl, triazolyl, imidazolyl, pyrazolyl and pyridinyl.
As used herein, an aromatic heterocycle in a substituent defined as "comprising a 5-or 6-membered aromatic heterocycle comprising at least one heteroatom selected from N, O, or S, preferably selected from N or S" may be optionally substituted with: a hydroxyl group; c (C) 1 -C 3 An alkoxy group; or oxo.
It will be understood that substitution of the aromatic heterocycle with oxo is intended to include (e.g., in a 1H-pyridin-2-one system) 5-or 6-membered rings in which an aromatic tautomer is present (see, e.g., example 92).
As used herein, the term "5-or 6-membered saturated heterocyclic ring" is used in reference to wherein R 5a And R is 5b Examples of the ring with the N atom to which they are attached (where N may also be NH) include, for example, but are not limited to:azetidinyl ring, pyrrolidine ring, or piperidine ring.
As used herein, the term "9-or 10-membered partially saturated heteroaryl group containing at least one N heteroatom" refers to a partially saturated aromatic bicyclic heterocyclic ring system in which a 5-or 6-membered heterocyclic ring containing one N heteroatom is fused to a benzene ring or heteroaromatic ring. In certain embodiments where N is present at the alpha position of the atom that binds Q to the rest of the molecule, this can be represented by the formula:or->Wherein the dashed ring represents a benzo ring or heteroaryl ring. Representative examples are indolinyl, isoindolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. Preferably, it is +.>Or (b)
As used herein, the term "optionally substituted" includes unsubstituted or substituted.
As used herein, the term "multiple" includes 2, 3, 4, 5, or 6 times. Preferably, it comprises 2 or 3 times.
The term "more than one" as used herein includes 2, 3, 4, 5, or 6. Preferably, it comprises 2 or 3.
As used herein, the term "at least one heteroatom" includes 1, 2, 3, 4 or 5, preferably 1, 2, 3 or 4, more preferably 1 or 2 heteroatoms.
The use of any and all examples, or exemplary language (e.g., "such as" or "preferably") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed.
As used herein, formula (la)The term nitrogen Protecting Group (PG) in compounds of formula (IV) and its subformulae refers to groups which should protect the relevant functional group from undesired secondary reactions such as acylation, etherification, esterification, oxidation, solvolysis and the like. It can be removed under deprotection conditions. Depending on the protecting group used, the skilled person will know how to remove the protecting group to obtain the free amine NH by referring to known procedures 2 A group. These include reference to textbooks and literature methods of organic chemistry, e.g., J.F.W.McOmie, "Protective Groups in Organic Chemistry [ protecting groups in organic chemistry ] ]", plenum Press [ Plenum Press ]]London and new york 1973; T.W.Greene and P.G.M.Wuts, "Greene's Protective Groups in Organic Synthesis [ protecting groups in Green organic Synthesis ]]"fourth edition, wiley [ Wiley Verlag]New york 2007; in "The Peptides]"; vol.3 (editions: E.Gross and J.Meienhofer), academic Press [ Academic Press ]]London and New York 1981 and "Methoden der organischen Chemie" (Methods of Organic Chemistry) [ methods of organic chemistry ]]Houben Weyl, 4 th edition, volume 15/I, georg Thieme Verlag [ Georgi Verlag]Stuttgart [ Stuttgart ]]1974, and subsequent versions thereof.
Preferred nitrogen protecting groups generally include: c (C) 1 -C 6 Alkyl (e.g., tert-butyl), preferably C 1 -C 4 Alkyl, more preferably C 1 -C 2 Alkyl, most preferably C 1 Alkyl, which is trialkylsilyl-C 1 -C 7 Alkoxy (e.g., trimethylsilylethoxy) mono-, di-, or trisubstituted;
aryl, preferably phenyl, or a heterocyclic group (e.g. benzyl, cumyl, benzhydryl, pyrrolidinyl, trityl, pyrrolidinylmethyl, 1-methyl-1, 1-dimethylbenzyl, (phenyl) methylbenzene), wherein the aryl ring or heterocyclic group is unsubstituted or substituted with one or more (e.g. two or three) residues, e.g. selected from the group consisting of: c (C) 1 -C 7 Alkyl, hydroxy, C 1 -C 7 Alkoxy (e.g., p-methoxybenzyl (PMB)), C 2 -C 8 Alkanoyl-oxy, halogen, nitro, cyano, and CF 3 ；
aryl-C 1 -C 2 Alkoxycarbonyl (preferably phenyl-C) 1 -C 2 Alkoxycarbonyl (e.g., benzyloxycarbonyl (Cbz), benzyloxymethyl (BOM), pivaloyloxymethyl (POM)), C 1 -C 10 -alkenyloxycarbonyl, C 1 -C 6 Alkylcarbonyl (e.g., acetyl or pivaloyl), C 6 -C 10 -an arylcarbonyl group; c (C) 1 -C 6 Alkoxycarbonyl groups (e.g., t-butoxycarbonyl (Boc), methylcarbonyl, trichloroethoxycarbonyl (Troc), pivaloyl (Piv), allyloxycarbonyl), C 6 -C 10 -aryl C 1 -C 6 Alkoxycarbonyl (e.g., 9-fluorenylmethoxycarbonyl (Fmoc)), allyl or cinnamyl, sulfonyl or sulfinyl, succinimidyl, silyl groups (e.g., triarylsilyl, trialkylsilyl, triethylsilyl (TES), trimethylsilylethoxymethyl (SEM), trimethylsilyl (TMS), triisopropylsilyl, or tert-butyldimethylsilyl).
According to the invention, the preferred Protecting Group (PG) may be selected from the group comprising: t-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), p-methoxybenzyl (PMB), methyloxycarbonyl and benzyl. The Protecting Group (PG) is preferably tert-butyloxycarbonyl (Boc).
The term "phenyl" refers to-C 6 H 5 Is a group of (2).
The term "halobenzodioxole" refers to a 1, 3-benzodioxole group of the formula:
wherein halo is as defined above. Preferably, both halo groups are fluoro.
The term "stereoisomers" refers to compounds having the same chemical constitution but different arrangements of atoms or groups in space.
The term "diastereoisomer" or "diastereomer" refers to a stereoisomer that is not related to the mirror image. Diastereoisomers are characterized by differences in physical properties and by some differences in chemical behavior. Mixtures of diastereomers can be separated under analytical procedures such as chromatography or crystallization.
The term "enantiomer" refers to one of a pair of molecular entities that are mirror images of each other and are non-overlapping.
The term "enantiomeric mixture" refers to a mixture of enantiomerically enriched, compositions comprising a greater proportion or percentage of one enantiomer of a compound of the invention relative to the other enantiomer or racemate.
The term "diastereomeric mixture" refers to a diastereomerically enriched mixture or an equal proportion of a mixture of diastereomers.
The term "diastereomerically enriched" refers to a composition comprising a greater proportion or percentage of one diastereomer of a compound of the invention relative to the other diastereomer or diastereomers.
The term "atropisomer" refers to stereoisomers resulting from a limited rotation about a single bond, wherein the rotation barrier is high enough to allow separation of isomeric species. Typically, because of the steric interactions with other parts of the molecule and the asymmetry of the substituents at both ends of the single bond, rotation about the single bond in the molecule is prevented or greatly slowed, resulting in the formation of a stereoisomerised source unit known as the "chiral axis".
As used herein, the term "YAP" refers to a yes-related protein, also known as YAP1 or YAP65.
Whenever YAP is referred to herein, it may also be referred to as YAP/TAZ complex.
As used herein, the term "YAP/TAZ-TEAD" refers to a complex of YAP/TAZ and TEAD transcription factors.
As used herein, the term "NF2/LATS1/LATS2" refers to "NF2", "LATS1", or "LATS2", or any combination thereof.
Any asymmetric atom (e.g., carbon or the like) of one or more compounds of the invention may exist in racemic or enantiomerically enriched form, e.g., (R) -, (S) -or (R, S) -configurations. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess in the (R) -or (S) -configuration. The substituents at the atoms having unsaturated double bonds may, if possible, be present in cis- (Z) -or trans- (E) -form.
Thus, as used herein, a compound present in any one of the combinations or methods disclosed herein may be in the form of one of the possible stereoisomers, rotamers, atropisomers, tautomers, or mixtures thereof, for example, as substantially pure geometric (cis or trans) stereoisomers, diastereomers, optical isomers (enantiomers), racemates, or mixtures thereof.
Any resulting mixture of stereoisomers may be separated into pure or substantially pure geometric or optical isomers, diastereomers, racemates based on the physicochemical differences of the components, for example by chromatography and/or fractional crystallization.
Any of the resulting racemates of the compounds or intermediates of the present invention may be resolved into the optical antipodes by known methods, for example by separating the diastereomeric salts thereof, obtained with optically active acids or bases, and liberating the optically active acidic or basic compounds. In particular, the basic moiety can thus be used to resolve the compounds of the invention into their optical enantiomers, for example by fractional crystallization with optically active acids such as tartaric acid, dibenzoyltartaric acid, diacetyltartaric acid, di-O, O' -p-toluyltartaric acid, mandelic acid, malic acid or camphor-10-sulphonic acid. The racemic compounds or racemic intermediates of the present invention can also be resolved by chiral chromatography (e.g., high Pressure Liquid Chromatography (HPLC) using chiral adsorbents).
The synthesis of compounds A, B, D, E, F and G and related TEAD inhibitors was initially described in PCT/IB2021/052136 (WO 2021/186324), the contents of which are incorporated by reference.
Combination examples
The method comprises the following steps:
for each of the cell lines in examples 11-38, the cells were dispensed into tissue culture treated 384 well plates (Greiner) # 781098) with a final volume of 25 μl/well. Cells were allowed to adhere and began to grow for twenty-four hours. Plates were counted prior to treatment (=day 1) and another plate was treated with compound or DMSO using HP D300 digital dispenser. Seventy-two hours later, the medium was refreshed by supplementing each well with 25 μl of medium containing the corresponding compound or DMSO. All treatments were performed in triplicate.
Seven days after the start of treatment, use(Promega, #G7573) cell growth was determined and the reagent was used to measure the amount of ATP in wells. The plate was equilibrated to room temperature for about thirty minutes and a volume of +.>And (3) a reagent. Cells were induced to lyse for two minutes on an orbital shaker, plates were incubated for ten minutes at room temperature, and luminescence was recorded.
Cells were treated with the compound at the indicated final concentrations. A XLfit dose response unit point model 205 is used to derive a dose response curve. Reported is the percentage of growth inhibition relative to DMSO (percent GI) after subtracting the day 1 reading.
Example 1: anti-tumor efficacy of TEAD inhibitors in combination with KRAS G12C inhibitors in H2122 and 2094-HX mouse xenograft models.
Compound C and AMG510 (sotoracicb) from the mecianin company are potent, selective and irreversible inhibitors of the mutant KRAS G12C protein. In these studies (fig. 1), the antitumor activity and tolerability of TEAD inhibitor compound a, compound C and sotoraciclovir (AMG 510) KRAS G12C inhibitors and combinations thereof were evaluated in two mouse xenograft models. H2122 is a human lung cancer cell line, and 2094-HX is a patient-derived xenograft (PDX) lung cancer model. KRAS of both cancer models are mutated and both carry G12C mutations. Treatment with single agent compound a at the concentrations indicated did not induce stasis or tumor regression in the H2122 tumor model. However, anti-tumor efficacy was observed with compound C or AMG510 KRAS G12C inhibitors, both agents inducing stasis in H2122 and tumor regression in the PDX model during treatment when administered as a single agent. In both experiments, a deeper tumor response was observed with the combination of compound a and KRAS G12C inhibitor. In particular, complete tumor regression was observed in the 2094-HX study combination group. Interestingly, most 2094-HX tumors treated with the combination remained undetectable after treatment ceased for more than 11 weeks. Body weight remained within normal range during the course of these experiments, with good tolerability.
Example 2: combination of TEAD inhibitors with KRAS G12C inhibitors for mutant colorectal PDX cancer models
The (KRAS) G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRAS G12C was identified as a potential drug target and predictor of response to KRAS G12C inhibitors. However, the response rate and overall survival benefits of such treatments remain limited. Here we assessed the potential benefit of the combination of KRASG12C inhibitor compound C with YAP/TAZ-TEAD inhibitor compound a. Compound a strongly disrupts protein-protein interactions between YAP1/WWTR1 and all four TEAD isoforms, thereby eliminating the transcriptional activity of the complex. From in vitro assays and preclinical experiments not shown, it is known that such YAP/TAZ-TEAD inhibitors are ineffective as single agents against CRC tumor models.
Compound a and/or compound C drug activity was evaluated in a patient-derived xenograft (PDX) model implanted in nude mice using an MCT (mouse clinical trial) protocol (fig. 2). These PDX models were derived from 9 different CRC patients. The same PDX model was implanted into nude mice. After randomized, one mouse was treated daily with compound C and the other with compound c+compound a. Two other mice were untreated and served as controls. Significant tumor response was observed when mice carrying xenograft models were treated daily with 100mg/kg of compound C. The anti-tumor effect is more prominent, and the tumor growth is reduced by 2.4 times by using the combination of the compound C and the compound A. See fig. 2.
Example 3: anti-tumor efficacy of TEAD inhibitors in combination with SHP2 inhibitors in mesothelioma and lung cancer mouse xenograft models
TNO155 is an original wild-type SHP2 allosteric inhibitor that prevents transduction of signaling from an activated RTK to the downstream RAS/MAPK pathway. The combination of TEAD inhibitor and SHP2 inhibitor (TNO 155) was evaluated in breast malignancy (fig. 3). Heterozygous KRAS G12C lung cancer xenograft model Lu99 and malignant pleural mesothelioma cancer xenograft model ACC-MESO1 were used for efficacy studies in mice. Although mild to good anti-tumor responses were observed with a single agent, the combination produced better results with observed tumor arrest or regression. All treatments were well tolerated and no weight loss was observed. These results demonstrate that a combination of SHP2 and TEAD inhibitor is beneficial in combating these malignancies.
Example 4: triple combination of TEAD inhibitor, SHP2 inhibitor and KRAS G12C inhibitor for Lu99 lung cancer xenograft model
Two-by-two and triple combination therapies of i) TEAD inhibitor, ii) SHP2 inhibitor and iii) KRAS G12C inhibitor were evaluated (fig. 4). Heterozygous KRAS G12C lung cancer xenograft model Lu99 was used for efficacy studies in nude mice. Compound a and compound B TEAD inhibitors were evaluated in two independent studies in 28 day and 22 day treatments, respectively. Animals were further monitored after cessation of treatment to observe tumor regrowth. In both experiments, the triple combination regimen showed complete regression. Body weight remained within normal range during the course of these experiments, with good tolerability.
Example 5:
the combination of the pan Raf inhibitor LHX254 and the MEK1/2 inhibitor trametinib was tested clinically in MAPK mutant cancers. The potentially beneficial anti-tumor effects of the triple combination of TEAD inhibitor (compound F) with LHX254 and trimetinib on lung cancer tumors were evaluated herein (fig. 5). Two KRAS mutant lung cancer xenograft models Lu99 and 2094-HX were used for efficacy studies in mice. Although tumor arrest was observed with LHX 254/trimetinib therapy, the triple combination with TEAD inhibitor produced better results and tumor regression was observed. All treatments were generally tolerated with only modest weight loss observed when the triple combination was used. These results demonstrate the potential therapeutic benefit of adding YAP/TAZ-TEAD inhibitors to LHX254 and trametinib treatment to combat malignancy.
Example 6:
combinations of pan-Raf inhibitors LHX254 and ERK1/2 active LTT462 inhibitors were tested clinically in MAPK mutant cancers.
The potentially beneficial anti-tumor effects of a combination of a TEAD inhibitor and LHX254/LTT462 therapy on lung cancer tumors were evaluated herein (FIG. 6).
NCI-H2052 malignant pleural mesothelioma cancer xenograft model was used for pharmacological studies in mice. Slight (compound a) to worse (LHX 254/LTT 462) anti-tumor responses were observed using simple targeted therapies, however, the combination of these three agents produced better results with tumor regression observed in KRAS G12C lung cancer xenograft mouse model 2094-HX (fig. 6-a). The antitumor effect of the targeted therapy compound A or LHX254/LTT462 was not apparent. In contrast, the triple combination caused sustained tumor arrest (fig. 6-B).
PDAC Mouse Clinical Trials (MCT) were performed using a medium dose of 90mg/kg daily of a combination of compound F (2- ((2S, 3S) -5-chloro-6-fluoro-2- ((((1 r, 4S) -4-hydroxy-4-methylcyclohexyl) amino) methyl) -3-methyl-2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4- ((S) -2-hydroxypropoxy) benzamide) and MAPKi LHX254/LTT462 (fig. 6-C). Even though these pancreatic tumors were generally refractory to treatment, 11 responders out of 23 (5 tumor arrests, 6 tumor regressions) were used in a triple combination. Also, other PDX models considered non-responders often show reduced tumor progression. Overall, these results demonstrate the potential therapeutic benefit of adding TEAD inhibitors to LHX254/LTT462 treatment to combat malignancy.
Example 7:
BRAFV600E mutations are found in 8% -10% of metastatic colorectal cancer (CRC) patients and are considered a poor prognostic factor with a median overall survival of less than 20 months (cancer [ cancer ] (Basel). 1 month 2021; 13 (1): 137.).
One strategy is to target the MAPK pathway by the application of dabraf BRAF mutation inhibitors and concomitant MAPK inhibitors (i.e., MEK, RAF and/or ERK inhibitors).
The potentially beneficial anti-tumor effects of the triple combination of TEAD inhibitor with dabrafenib and LTT462 on lung cancer tumors were evaluated herein in a mouse efficacy study using HT-29CRC xenograft model (fig. 7).
Although little tumor response was observed in response to Yu Dala non-ni/LTT 462 combination therapy, the triple combination with TEAD inhibitors produced better results, extending tumor arrest. Compound a was used at 100mg/kg for 2 weeks and the dose increased to 200mg/kg for 2 weeks due to acceptable tolerability. These treatments were well tolerated and no weight loss was observed. These results demonstrate the potential therapeutic benefit of adding YAP/TAZ-TEAD inhibitors to the radenib/LTT 462 treatment to combat malignancy.
Example 8:
BRAFV600E mutations are found in 8% -10% of metastatic colorectal cancer (CRC) patients and are considered a poor prognostic factor with a median overall survival of less than 20 months (cancer [ cancer ] (Basel). 1 month 2021; 13 (1): 137.). One of the strategies in the art is to target the MAPK pathway by applying dabraf BRAF mutation inhibitors and concomitant MAPK inhibitors (i.e., MEK, RAF and/or ERK inhibitors). It is theorized herein that additional inhibition of TEAD transcription factors may provide an attractive therapy to improve the anti-tumor response.
The potentially beneficial anti-tumor effects of the triple combination of TEAD inhibitor and dabrafenib/trimetinib therapy on colorectal cancer tumors were evaluated (fig. 8). 5238-HX PDX murine model and HT-29 rat xenograft model were used for pharmacological studies.
The anti-tumor efficacy against xenografts implanted from PDX model 5238-HX was evaluated. Triple therapy of dabrafenib, trametinib and anti-EGFR antibodies such as cetuximab and the like is one of the presently preferred combinations in CRC (Ann oncology yearbour 2016;27 (journal_6): 4550.). In this context, this triple combination was compared with the combination of darafinib, trametinib and TEAD inhibitor (compound F) in mice. In this particular model, blocking TEAD was found to be more beneficial than blocking EGFR in addition to darifenacin/trimetinib.
Reference is made to: corcoran RB, andreT, yoshino T et al Efficacy and circulating tumor DNA (ctDNA) analysis of the BRAF inhibitor dabrafenib (D), MEK inhibitor trametinib (T), and anti-EGFR antibody panitumumab (P) in components (pts) with BRAF V600E-mutated (BRAFm) metastatic colorectal cancer (mCRC) [ BRAF inhibitor Darafenib (D), MEK inhibitor trametinib (T) and anti-EGFR antibody panitumumab (P) efficacy in BRAF V600E mutant (BRAFm) metastatic colorectal cancer (mCRC) patients (pts) and circulating tumor DNA (ctDNA) analysis ] Ann Oncol [ annual oncology ]2016;27 (journal_6): 4550.
In the HT-29 rat model, dabrafenib/trimetinib therapy caused 34% tumor regression after 16 days. The addition of TEAD inhibitor compound A (used at a weekly dose of 210mg/kg, 30mg/kg daily) slightly improved the response (-41% tumor regression). To be able to increase the dose/effect of compound a in rats without causing tolerability problems we used an intermittent dosing regimen of 300mg/kg administered weekly: 100mg/kg administered for 3 days/4 days of inactivity regimen. At this higher dose, a deeper regression of-73% was observed on day 16.
These results demonstrate the potential therapeutic benefit of adding YAP/TAZ-TEAD inhibitors to the radenib/trimetinib treatment to combat malignancy.
Example 9:
the anti-tumor efficacy of simultaneous inhibition of TEAD (using compound a or compound B) and cMET inhibition (using INC 280/carbamatinib) was investigated using the syngeneic mouse model (fig. 9) 24284-MA.
24284-MA allograft tumor model developed by North Co., ltd, is a spontaneous tumor derived from genetically engineered mouse strains with Arf null mutations, and thus also leads to copy number changes. It was identified as a spindle cell sarcoma with Met gene amplification. Mice were treated for 13 days and then monitored for recovery. TEAD inhibitor compound a has limited effect as a single agent, but with compound B, tumor stasis was observed in the treatment. After cessation of treatment, the tumor growth rate increases. The cMET inhibitor carbamazepine produced a deep regression (-70.3%) as a single agent, day 13. However, the combination of carbamazepine with either compound a or compound B resulted in an enhanced response (90.6% and 88.6%, respectively, day 13). After cessation of treatment, the tumor recovery growth time of the combination regimen was longer compared to monotherapy.
Example 10:
the TEAD inhibitor compound G (2- ((2 s,4 s) -5-chloro-6-fluoro-2- ((((1 r,4 s) -4-hydroxycyclohexyl) amino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -4- (difluoromethoxy) -3-fluorobenzamide) was used in combination with EGFR inhibitor EGF816 for lung cancer cell line PC9 with an activated EGFR mutation. PC9 cells were found to be insensitive to compound G single agent treatment up to 100nM (fig. 10A) but were strongly inhibited by EGF816 single agent treatment for up to 15 days (fig. 10A), after which proliferation was restored while still continuously exposed to EGF816 (fig. 10b, EGF816 300 nM). The combination of compound G with EGF816 showed dose-dependent benefits and completely prevented the occurrence of cell regrowth observed with EGF816 as a single agent (fig. 10b,816+qhs10-30-100 nM).
Example 11:
after 6 days of treatment with TEAD inhibitor (compound a or compound B) in combination with PI3K inhibitor QAU421 (BYL 719/analog of apicalist/Piqray), the celltiter glo assay was used to assess the in vitro viability of MCF7 breast cancer cell lines (PIK 3CA mutants). Minimal growth inhibition was observed with compound a or compound B single agent treatment (up to 3uM, fig. 11A-B). In contrast, the combination of compound a or compound B with QAU421 resulted in a dose dependent induction of cell death.
Example 12:
after 6 days of treatment with various combinations of TEAD inhibitor compound D in combination with MAPK pathway inhibitors (MEK inhibitor MEKINIST/trimetinib/CFF 272, BRAF/CRAF inhibitor LXH254 and ERK inhibitor LTT 462), the in vitro viability of the lung KRAS G12C mutant cell line LU-99 was assessed using the celltiter glo assay. Either compound d+cff272 or compound d+ltt462 in combination was sufficient to induce cell death at concentrations where a single agent promoted cell growth retardation (fig. 12A-B). In the case of triple combination with the BRAF/CRAF inhibitor LXH254, the combined benefit was enhanced with deeper MAPK inhibition (fig. 12C-D).
Example 13:
after 6 days of treatment with various combinations of TEAD inhibitor compound E in combination with MAPK pathway inhibitors (BRAF inhibitor tafinal/dabrafenib/LIQ 288, MEK inhibitor MEKINIST/trimetinib/CFF 272, BRAF/CRAF inhibitor LXH254 and ERK inhibitor LTT 462), the in vitro viability of the pulmonary BRAF mutant colorectal cell line SW-1417 was assessed using CellTiterGlo assay. The triple combinations involving compound e+liq288+cff272 (fig. 13A), compound e+lxh254+cff272 (fig. 13B) and compound e+lxh254+ltt462 (fig. 13C) were all sufficient to induce cell death at concentrations where compound E alone or in combination with a two-way MAPK induced cell growth retardation (fig. 13A-B).
Example 14:
after 3 days of treatment with TEAD inhibitor compound D in combination with p53-HDM2 inhibitor HDM201, the CDKN 2A-deleted mesothelioma cell line MSTO-211H was evaluated for in vitro viability using the CellTiterGlo assay. Combined benefits were observed at sub-effective concentrations of single agents (fig. 14).
Example 15:
after 3 days of treatment with TEAD inhibitor compound D in combination with CDK4/6 inhibitor LEE011, mesothelioma cell line MSTO-211H was assessed for in vitro viability using celltiter glo assay. MSTO-211H was not sensitive to LEE011 single agent treatment, but combined benefit was observed at sub-effective concentrations of compound D (fig. 15).
Example 16:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of HCC44 cells, and compound a also showed single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 17:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor sotoracib and (ii) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor sotoracib and the SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of HCC44 cells, and compound a also showed single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 18:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb, (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155, and (iii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Adaglazeb alone or adaglazeb+rmc-4550 inhibited proliferation of HCC44 cells, and compound a also showed single agent activity. In comparison, combinations (i), (ii) and (ii) show synergistic growth inhibition.
Example 19:
after 7 days of treatment with YAP/TEAD inhibitor compound A in combination with SHP2 inhibitor TNO-155, the lung cancer cell line HCC44 was assessed for viability in vitro using CellTiterGlo. TNO155 did not significantly inhibit HCC44 cell proliferation at the concentrations tested, whereas compound a showed single agent activity. The combination showed synergistic growth inhibition compared to either treatment alone. Combinations of YAP/TEAD inhibitor compound A and SHP2 inhibitor RMC-4550 (not shown in FIG. 19) were also tested. This combination is also synergistic.
Example 20:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of HCC44 cells, and compound B also showed single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 21:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound B in combination with the KRAS G12C inhibitor sotoracib and (ii) the YAP/TEAD inhibitor compound B in combination with the KRAS G12C inhibitor sotoracib and the SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of HCC44 cells, and compound B also showed single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 22:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb, (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155, and (iii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Adaglazeb alone and adaglazeb+rmc-4550 inhibited proliferation of HCC44 cells, and compound B also showed single agent activity. In comparison, combinations (i), (ii) and (ii) show synergistic growth inhibition.
Example 23:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO-155, the lung cancer cell line HCC44 was assessed for viability in vitro using CellTiterGlo. TNO155 did not significantly inhibit proliferation of HCC44 cells, whereas compound B showed single agent activity. In comparison, the combination showed synergistic growth inhibition compared to either treatment alone. Combinations of YAP/TEAD inhibitor compound B and the SHP2 inhibitor RMC-4550 (not shown in FIG. 23) were also tested. This combination is also synergistic.
Example 24:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. JDQ443, JDQ443+tno155 and compound H inhibited the proliferation of HCC44 cells, and synergistic combined benefits were observed in (i) and (ii).
Example 25:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor sotoracib and (ii) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor sotoracib and the SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC44 was assessed using CellTiterGlo. Sotoprazole, sotoprazole+tno 155 and compound H inhibited proliferation of HCC44 cells, and synergistic combined benefits were observed in (i) and (ii).
Example 26:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor adaglazeb and (ii) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor adaglazeb and the SHP2 inhibitor RMC-4550, the in vitro viability of lung cancer cell line HCC44 was assessed using celltiter glo. Adaglazeb, adaglazeb+tno 155 and compound H inhibited HCC44 cell proliferation, and synergistic combined benefits were observed in (i) and (ii).
Example 27:
colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO 155. JDQ443 and JDQ443+tno155 alone inhibited proliferation of SW1463 cells, and compound a also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 28:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor sotoracicb and (ii) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor sotoracicb and the SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of SW1463 cells, and compound a also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 29:
colorectal cancer cell line SW1463 was assessed using celltiter glo after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb, (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155, and (iii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550. Adaglazeb, adaglazeb+tno 155 and adaglazeb+rmc-4550 inhibited proliferation of SW1463 cells, and compound a also showed some single agent activity. In comparison, combinations (i), (ii) and (iii) showed synergistic growth inhibition compared to either treatment alone.
Example 30:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO-155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using celltiter glo. TNO-155 does not inhibit SW1463 cell proliferation at the concentrations tested, whereas Compound A shows some single agent activity. In comparison, the combination showed synergistic growth inhibition compared to either treatment alone. Combinations of YAP/TEAD inhibitor compound A and SHP2 inhibitor RMC-4550 (not shown in FIG. 30) were also tested. This combination is also synergistic.
Example 31:
colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO 155. JDQ443 and JDQ443+tno155 alone inhibited proliferation of SW1463 cells, and compound B also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 32:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound B in combination with the KRAS G12C inhibitor sotoracicb and (ii) the YAP/TEAD inhibitor compound B in combination with the KRAS G12C inhibitor sotoracicb and the SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of SW1463 cells, and compound B also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 33:
colorectal cancer cell line SW1463 was assessed using celltiter glo after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb, (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor TNO155, and (iii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550. Adaglazeb, adaglazeb+tno 155 and adaglazeb+rmc-4550 inhibited proliferation of SW1463 cells, and compound B also showed some single agent activity. In comparison, combinations (i), (ii) and (iii) showed synergistic growth inhibition compared to either treatment alone.
Example 34:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO-155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using celltiter glo. TNO-155 alone did not inhibit SW1463 cell proliferation at the concentrations tested, whereas Compound B showed some single agent activity. In comparison, the combination showed synergistic growth inhibition compared to either treatment alone. Combinations of YAP/TEAD inhibitor compound B and the SHP2 inhibitor RMC-4550 (not shown in FIG. 34) were also tested. This combination is also synergistic.
Example 35:
colorectal cancer cell line SW1463 was assessed for viability in vitro using celltiter glo after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO 155. JDQ443 and JDQ443+tno155 alone inhibited proliferation of SW1463 cells, whereas compound H showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 36:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor sotoracicb and (ii) the YAP/TEAD inhibitor compound H in combination with the KRAS G12C inhibitor sotoracicb and the SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of SW1463 cells, and compound H also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 37:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb, and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor adaglazeb and SHP2 inhibitor RMC-4550, the in vitro viability of colorectal cancer cell line SW1463 was assessed using CellTiterGlo. Adaglazeb alone and adaglazeb+rmc-4550 inhibited proliferation of SW1463 cells, and compound H also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 38:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor compound C and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor compound C and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Compound C alone and compound c+tno155 inhibited proliferation of NCI-H2122 cells, and compound a also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 39:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor compound C and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor compound C and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Compound C alone and compound c+tno155 inhibited proliferation of NCI-H2122 cells, and compound B also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 40:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor compound C and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor compound C and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H2122 was assessed using celltiter glo. Compound C alone and compound c+tno155 inhibited proliferation of NCI-H2122 cells, and compound H also showed some single agent activity. In comparison, the combination (i) and (ii) showed synergistic growth inhibition compared to either treatment alone.
Example 41:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of NCI-H1373 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 42:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Compound a inhibited proliferation of NCI-H1373 cells and TNO155 also showed some single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 43:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of NCI-H1373 cells, and compound B also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 44:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Compound B alone inhibited proliferation of NCI-H1373 cells and TNO155 also showed some single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 45:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H1373 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of NCI-H1373 cells, and compound H also showed some single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 46:
after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H1373 was assessed for viability in vitro using celltiter glo. Compound H alone inhibited proliferation of NCI-H1373 cells and TNO155 also showed some single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 47:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of HCC-1171 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 48:
after 7 days of treatment with YAP/TEAD inhibitor compound A in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. Compound a inhibited the proliferation of HCC-1171 cells, and TNO155 also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 49:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of HCC-1771 cells, and compound B also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 50:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. Compound B alone inhibited proliferation of HCC-1171 cells, and TNO155 also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 51:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line HCC-1171 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of HCC-1171, and compound H also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 52:
after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line HCC-1171 was assessed for viability in vitro using CellTiterGlo. TNO155 alone inhibited proliferation of HCC-1171 cells, and Compound H also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 53:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of NCI-H358 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 54:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. TNO155 alone inhibited proliferation of NCI-H358 cells, and Compound A also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 55:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of NCI-H358 cells, and compound B also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 56:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. Compound B alone inhibited proliferation of NCI-H358 cells, and TNO155 also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 57:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line NCI-H358 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of NCI-H358 cells, and compound H also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 58:
after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the lung cancer cell line NCI-H358 was assessed for viability in vitro using celltiter glo. TNO155 alone inhibited proliferation of NCI-H358 cells, and Compound H also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 59:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib, and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor sotoracib and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line LU65 was assessed using CellTiterGlo. Sotorubin alone and sotorubin+tno 155 inhibited proliferation of LU65 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 60:
after 7 days of treatment with (i) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor adaglazeb, and (ii) the YAP/TEAD inhibitor compound a in combination with the KRAS G12C inhibitor adaglazeb and the SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line LU65 was assessed using CellTiterGlo. Adaglazeb alone and adaglazeb+tno 155 inhibited proliferation of LU65 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 61:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443, the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. JDQ443 inhibits proliferation of LU65 cells, and compound a also shows single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone. The combination of jdq443+tno155 and YAP/TEAD inhibitor compound a (not shown in fig. 61) was also tested. This combination is also synergistic.
Example 62:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ443, the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. JDQ443 inhibits proliferation of LU65 cells, and compound B also shows single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone. The combination of jdq443+tno155 and YAP/TEAD inhibitor compound B (not shown in fig. 62) was also tested. This combination is also synergistic.
Example 63:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of lung cancer cell line LU65 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of LU65 cells, and compound H also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 64:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of the SW837 cell line, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 65:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. TNO155 inhibited proliferation of SW837 cell line, and compound a also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 66:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of SW837 cells, and compound B also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 67:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. TNO155 inhibited proliferation of SW837 cells, and compound B also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 68:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of SW837 cells, and compound H also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 69:
after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line SW837 was assessed using celltiter glo. TNO155 inhibited proliferation of SW837 cells, and compound H also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 70:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound a in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibited proliferation of LIM2099 cells, and compound a also showed single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 71:
after 7 days of treatment with YAP/TEAD inhibitor compound a in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. TNO155 inhibited proliferation of LIM2099 cells, and compound a also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 72:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound B in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of LIM2099 cells, and compound B also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 73:
after 7 days of treatment with YAP/TEAD inhibitor compound B in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. TNO155 inhibited proliferation of SW837 cells, and compound B also showed single agent activity. In comparison, the combination showed synergistic activity compared to either treatment alone.
Example 74:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and (ii) YAP/TEAD inhibitor compound H in combination with KRAS G12C inhibitor JDQ-443 and SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. JDQ443 and JDQ443+tno155 alone inhibit proliferation of LIM2099 cells, and compound H also shows single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.
Example 75:
after 7 days of treatment with YAP/TEAD inhibitor compound H in combination with SHP2 inhibitor TNO155, the in vitro viability of colorectal cancer cell line LIM2099 was assessed using celltiter glo. TNO155 inhibited proliferation of LIM2099 cells, and compound H also showed single agent activity. In comparison, the combination showed synergistic activity compared to the monotherapy.
Example 76:
after 7 days of treatment with (i) YAP/TEAD inhibitor compound a in combination with CDK4/6 inhibitor NVP-LEE011 (LEE 011 or rebamacinib), and (ii) YAP/TEAD inhibitor compound a in combination with CDK4/6 inhibitor NVP-LEE011 (LEE 011 or rebamacinib), and KRAS G12C inhibitor JDQ443, the in vitro viability of lung cancer cell line NCI-H1792 was assessed using cyquat. LEE011 and jdq443+ compound a alone inhibited proliferation of NCI-H1792 cells, and compound a alone also showed some single agent activity. In comparison, combinations (i) and (ii) showed synergistic activity compared to either treatment alone.

Claims (56)

1. A method of treating cancer in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a TEAD inhibitor in combination with a first additional therapeutically active agent and optionally a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
2. A TEAD inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a first additional therapeutically active agent and optionally a second therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
3. A combination, comprising: i) TEAD inhibitors, ii) a first additional therapeutically active agent, and optionally iii) a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of: KRAS G12/G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, raf inhibitors, CDK4/6 inhibitors, and cMET inhibitors.
4. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is a KRAS G12/G13 inhibitor (e.g., KRAS G12C inhibitor), e.g., when the second therapeutically active agent is absent.
5. The method of claim 4, the TEAD inhibitor for use of claim 4, or the combination of claim 4, wherein the second additional therapeutically active agent is present and is an SHP2 inhibitor.
6. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is an SHP2 inhibitor, e.g., when the second therapeutically active agent is absent.
7. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is an EGFR inhibitor, e.g., when the second therapeutically active agent is not present.
8. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is a PI3K inhibitor, e.g., when the second therapeutically active agent is absent.
9. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is an MDM2 inhibitor, e.g., when the second therapeutically active agent is absent.
10. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is a CDK4/6 inhibitor, e.g., when the second therapeutically active agent is absent.
11. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is a MEK inhibitor, e.g., when the second therapeutically active agent is absent.
12. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is an ERK inhibitor, e.g., when the second therapeutically active agent is absent.
13. The method of claim 11 or claim 12, the TEAD inhibitor for use of claim 11 or claim 12, or the combination of claim 11 or claim 12, wherein a second additional therapeutically active agent is present, and wherein the second additional therapeutically active agent is a Raf inhibitor.
14. The method of claim 1, the TEAD inhibitor for use of claim 2, or the combination of claim 3, wherein the first additional therapeutically active agent is a cMET inhibitor, e.g., when the second therapeutically active agent is not present.
15. A cMET inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
16. A KRAS G12/G13 inhibitor (e.g., a KRAS G12C inhibitor) for use in cancer treatment, wherein the treatment further comprises administration of a TEAD inhibitor.
17. The KRAS G12/G13 inhibitor for use of claim 16 wherein the treatment further comprises administration of an SHP2 inhibitor.
18. An SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
19. The SHP2 inhibitor for use of claim 18, wherein the treatment further comprises administration of a KRAS G12/G13 inhibitor (e.g., a KRAS G12C inhibitor).
20. A MEK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
21. An ERK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
22. The MEK inhibitor for use of claim 20 or the ERK inhibitor for use of claim 21, wherein the treatment further comprises administration of a Raf inhibitor.
23. A Raf inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
24. The Raf inhibitor for use of claim 23, wherein the treatment further comprises administration of a MEK inhibitor.
25. The Raf inhibitor for use according to claim 23, wherein the treatment further comprises administration of an ERK inhibitor.
26. An EGFR inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
27. A PI3K inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.
28. An MDM2 inhibitor for use in cancer treatment, wherein the treatment further comprises administration of a TEAD inhibitor.
29. A CDK4/6 inhibitor for use in the treatment of cancer, wherein said treatment further comprises administering a TEAD inhibitor.
30. The method of any one of claims 1 and 4 to 14, the TEAD inhibitor of any one of claims 2 and 4 to 14, the combination of any one of claims 3 to 14, the cMET inhibitor of claim 15, the KRAS G12/G13 inhibitor of claim 16 or claim 17, the SHP2 inhibitor of claim 18 or claim 19, the MEK inhibitor of claim 20 or claim 22, the ERK inhibitor of claim 21 or claim 22, the Raf inhibitor of any one of claims 23 to 25, the EGFR inhibitor of claim 26, the PI3K inhibitor of claim 27, the MDM2 inhibitor of claim 28, or the MDM 4/6 inhibitor of claim 29, wherein the TEAD inhibitor is a YAP/TAZ-protein-TEAD interaction inhibitor.
31. The method of claim 30, the TEAD inhibitor of claim 30, the combination of claim 30, the cMET inhibitor of claim 30, the KRAS G12/G13 inhibitor of claim 30, the SHP2 inhibitor of claim 30, the MEK inhibitor of claim 30, the ERK inhibitor of claim 30, the Raf inhibitor of claim 30, the EGFR inhibitor of claim 30, the PI3K inhibitor of claim 30, the MDM2 inhibitor of claim 30, or the CDK4/6 inhibitor of claim 30, wherein the TEAD inhibitor is a TEAD inhibitor of formula (I), or a pharmaceutically acceptable salt thereof, e.g., compound A (4- ((2S, 4S) -5-chloro-6-fluoro-2-phenyl-2- ((S) -pyrrolidin-2-yl) -2, 3-dihydro-benzofuran-6-hydroxy-methyl-2- (2-ethoxy) -5-hydroxy-2-methyl-ethoxy) -2-N-methyl-2-ethoxy-2-N-methyl-2-hydroxy-ethoxy-2-N-methyl-2, or compound B (2- ((2 s,3s,4 s) -5-chloro-6-fluoro-3-methyl-2- ((methylamino) methyl) -2-phenyl-2, 3-dihydrobenzofuran-4-yl) -3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof.
32. The method of any one of claims 1, 4, 5, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 5, 30 and 31, the combination of any one of claims 3 to 5, 30 and 31, the KRAS G12/G13 inhibitor for use of any one of claims 16, 17, 30 and 31, or the SHP2 inhibitor for use of any one of claims 19, 30 and 31, wherein the KRAS G12/G13 inhibitor is a KRAS G12C inhibitor selected from the group consisting of: compound C, sotoracicb (mecianin), adaglazeb (Mirati), D-1553 (benefit organism), BI1701963 (bringer), GDC6036 (roc), JNJ74699157 (prednisone), X-Chem KRAS (X-Chem), LY3537982 (gili), BI1823911 (bringer), AS KRAS G12C (flourishing pharmaceutical company), SF KRAS G12C (cerofil company), RMC032 (revolutionary pharmaceutical company), JAB-21822 (additive pharmaceutical company), AST-KRAS G12C (Ai Lisi pharmaceutical company), AZ KRAS G12C (aslicang company), NYU-12VC1 (new york university) and RMC6291 (revolutionary pharmaceutical company), or pharmaceutically acceptable salts thereof.
33. The method of claim 32, the TEAD inhibitor for use of claim 32, the combination of claim 32, the KRAS G12/G13 inhibitor for use of claim 32, or the SHP2 inhibitor for use of claim 32, wherein the KRAS G12/G13 inhibitor is the KRAS G12C inhibitor compound C (1- {6- [ (4M) -4- (5-chloro-6-methyl-1H-indazol-4-yl) -5-methyl-3- (1-methyl-1H-indazol-5-yl) -1H-pyrazol-1-yl ] -2-azaspiro [3.3] heptan-2-yl } prop-2-en-1-one) or AMG510, or a pharmaceutically acceptable salt thereof.
34. The method of claim 33, the TEAD inhibitor for use of claim 33, the combination of claim 33, the KRAS G12/G13 inhibitor for use of claim 33, or the SHP2 inhibitor for use of claim 33, wherein the KRAS G12/G13 inhibitor is the KRAS G12C inhibitor compound C, or a pharmaceutically acceptable salt thereof.
35. The method of any one of claims 1, 5, 6 and 30 to 34, the TEAD inhibitor for use of any one of claims 2, 5, 6 and 30 to 34, the combination of any one of claims 3, 5, 6 and 30 to 34, the KRAS G12/G13 inhibitor for use of any one of claims 17 and 30 to 34, or the SHP2 inhibitor for use of any one of claims 18, 19 and 30 to 34, wherein the SHP2 inhibitor is selected from the group consisting of: TNO155 (North Co., ltd.), JAB3068 (Gasci Co., ltd.), JAB3312 (Gasci Co., ltd.), RLY1971 (Roche Co.), SAR442720 (Sainofil Co., ltd.), RMC4550 (Innovative Co., ltd.), RMC4630 (Innovative Co., ltd.), BBP398 (Navire Co., ltd.), BR790 (Shanghai green and Moss medical science Co., ltd.), SH3809 (Nanj holy and Co., ltd.), PF0724982 (Condui Co., ltd.), ERAS601 (Erasca Co., ltd.), RX-SHP2 (Redx Co., ltd.), ICP189 (Nocheng, santa Clara Co., ltd.), HBI2376 (Shanghai Co., ltd.), ETS001 (Shanghai biological pharmaceutical Co., ltd.), TAS-ASTX (Datsukamura pharmaceutical Co., ltd.) and X-37-SHP2 (X-37), or a pharmaceutically acceptable salt thereof.
36. The method of claim 35, the TEAD inhibitor for use of claim 35, the combination for use of claim 35, the KRAS G12/G13 inhibitor for use of claim 35, or the SHP2 inhibitor for use of claim 35, wherein the SHP2 inhibitor is TNO155, or a pharmaceutically acceptable salt thereof.
37. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the cMET inhibitor for use of claim 15, wherein the cMET inhibitor is selected from the group consisting of: crizotinib, carbamazetinib, terpontinib, AMG337, cabotinib, certetinib (AZD 6094, HMPL-504), tivantinib, furitinib, wo Liti, SU11274, PHA 665752, SGX523, BAY-853474, KRC-408, T-1840383, MK-2461, BMS-777607, JNJ-38877605, tivantinib (ARQ 197), PF-04217403, MGCD265, BMS-754807, BMS-794833, AMG-458, NVP-BVU972, AMG-208, govatinib, norcantharidin, S49076, SAR125844, mexitinib (2801653), onabantuzumab, imatuzumab, SAIT301, ABT-700, DN30, LY3164530, rituximab, TAK and yybb-101, or pharmaceutically acceptable salts thereof.
38. The method of claim 37, the TEAD inhibitor for use of claim 37, the combination of claim 37, or the cMET inhibitor for use of claim 37, wherein the cMET inhibitor is: i) Terpontinib, or ii) carbamazepine, or a pharmaceutically acceptable salt thereof.
39. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the EGFR inhibitor for use of claim 26, wherein the EGFR inhibitor is selected from the group consisting of: cetuximab, panitumumab, erlotinib, gefitinib, oxtinib and nazatinib, or a pharmaceutically acceptable salt thereof.
40. The method of claim 39, the TEAD inhibitor for use of claim 39, the combination of claim 39, or the EGFR inhibitor for use of claim 39, wherein the EGFR inhibitor is nazatinib (also known as EGF 816), or a pharmaceutically acceptable salt thereof.
41. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the PI3K inhibitor for use of claim 27, wherein the PI3K inhibitor is selected from the group consisting of: AMG511, bupanii, erila, copani, du Weili sibutra, apirism, QAU421 and erbitux, or a pharmaceutically acceptable salt thereof.
42. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the MDM2 inhibitor for use of claim 28, wherein the MDM2 inhibitor is selected from the group consisting of: nutlin-3a, idanealin (also known as RG 7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, mi Lade maytansine and HDM201 (also known as sirodelin), or pharmaceutically acceptable salts thereof.
43. The method of claim 42, the TEAD inhibitor for use of claim 42, the combination of claim 42, or the MDM2 inhibitor for use of claim 42, wherein the MDM2 inhibitor is HDM201, or a pharmaceutically acceptable salt thereof.
44. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the CDK4/6 inhibitor for use of claim 29, wherein the CDK4/6 inhibitor is selected from the group consisting of: rebaudiana, palbociclib, and abbe west, or pharmaceutically acceptable salts thereof.
45. The method of claim 44, the TEAD inhibitor for use of claim 44, the combination of claim 44, or the CDK4/6 inhibitor for use of claim 44, wherein said CDK4/6 inhibitor is rebamactinib, or a pharmaceutically acceptable salt thereof.
46. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the MEK inhibitor for use of claim 20 or claim 22, or the Raf inhibitor for use of claim 24, wherein the MEK inhibitor is selected from the group consisting of: pimosaic, PD-0325901, semantenib, tramatinib, bemetinib and cobratinib, or pharmaceutically acceptable salts thereof.
47. The method of claim 46, the TEAD inhibitor for use of claim 46, the combination of claim 46, the MEK inhibitor for use of claim 46, or the Raf inhibitor for use of claim 46, wherein the MEK inhibitor is trametinib, or a pharmaceutically acceptable salt thereof.
48. The method of any one of claims 1, 14, 30 and 31, the TEAD inhibitor for use of any one of claims 2, 4, 30 and 31, the combination of any one of claims 3, 4, 30 and 31, or the ERK inhibitor for use of claim 21 or claim 22, or the Raf inhibitor for use of claim 25, wherein the ERK inhibitor is selected from the group consisting of: ulitinib, GDC-0994, KO-947, vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523, or pharmaceutically acceptable salts thereof.
49. The method of claim 48, the TEAD inhibitor for use of claim 48, the combination of claim 48, the ERK inhibitor for use of claim 48, or the Raf inhibitor for use of claim 48, wherein the ERK inhibitor is LTT462 (rilnetbase cloth) or ulitinib, or a pharmaceutically acceptable salt thereof.
50. The method of any one of claims 1, 14, 30, 31 and 46 to 49, the TEAD inhibitor for use of any one of claims 2, 4, 30, 31 and 46 to 49, the combination of any one of claims 3, 4, 30, 31 and 46 to 49, the MEK inhibitor for use of claim 22, the ERK inhibitor for use of claim 22, or the Raf inhibitor for use of any one of claims 23 to 25, wherein the Raf inhibitor is selected from the group consisting of: bei Fafei, naprafenib (also known as LXH 254), encofenib, vitamin Mo Feini and Darafenib, or pharmaceutically acceptable salts thereof.
51. The method of claim 50, the TEAD inhibitor for use of claim 50, the combination of claim 50, the MEK inhibitor for use of claim 50, the ERK inhibitor for use of claim 50, or the Raf inhibitor for use of claim 50, wherein the Raf inhibitor is dabrafenib or LXH254 (naprafenib), or a pharmaceutically acceptable salt thereof.
52. The method of any one of claims 1, 4 to 14 and 30 to 51, the TEAD inhibitor of any one of claims 2, 4 to 14 and 30 to 51, the cMET inhibitor of any one of claims 15, 30, 31, 37 and 38, the KRAS G12/G13 inhibitor of any one of claims 16, 17 and 30 to 36, the SHP2 inhibitor of any one of claims 18, 19 and 30 to 36, the MEK inhibitor of any one of claims 20, 22, 30, 31, 46, 47, 50 and 51, the ERK inhibitor for use of any one of claims 21, 22, 30, 31 and 48 to 51, the Raf inhibitor for use of any one of claims 23 to 25, 30, 31 and 46 to 51, the EGFR inhibitor for use of any one of claims 26, 30, 31, 39 and 40, the PI3K inhibitor for use of any one of claims 27, 30, 31 and 41, the MDM2 inhibitor for use of any one of claims 28, 30, 31, 42 and 43, or the CDK4/6 inhibitor for use of any one of claims 29 to 31, 44 and 45, wherein the cancer is a TEAD dependent cancer.
53. The method of any one of claim 1, 4 to 14 and 30 to 52, the TEAD inhibitor of any one of claim 2, 4 to 14 and 30 to 52, the cMET inhibitor of any one of claim 15, 30, 31, 37, 38 and 52, the KRAS G12/G13 inhibitor of any one of claim 16, 17, 30 to 36 and 52, the SHP2 inhibitor of any one of claim 18, 19, 30 to 36 and 52, the MEK inhibitor of any one of claim 20, 22, 30, 31, 46, 47 and 50 to 52, the ERK inhibitor for use of any one of claims 21, 22, 30, 31 and 48 to 52, the Raf inhibitor for use of any one of claims 23 to 25, 30, 31 and 46 to 52, the EGFR inhibitor for use of any one of claims 26, 30, 31, 39, 40 and 52, the PI3K inhibitor for use of any one of claims 27, 30, 31, 41 and 52, the MDM2 inhibitor for use of any one of claims 28, 30, 31, 42, 43 and 52, or the CDK4/6 inhibitor for use of any one of claims 29 to 31, 44, 45 and 52, wherein the cancer is selected from the group consisting of: breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma, head and neck cancer, sarcoma, squamous cell carcinoma, epithelioid vascular endothelial tumor, ependymal tumor and bone cancer.
54. The method of any one of claims 1, 4 to 14 and 30 to 53, the TEAD inhibitor for use of any one of claims 2, 4 to 14 and 30 to 53, the ERK inhibitor for use of any one of claims 15, 30, 31, 37, 38, 52 and 53, the Raf inhibitor for use of any one of claims 16, 17, 30 to 36, 52 and 53, the KRAS G12/G13 inhibitor for use of any one of claims 18, 19, 30 to 36, 52 and 53, the SHP2 inhibitor for use of any one of claims 20, 22, 30, 31, 46, 47 and 50 to 53, the MEK inhibitor for use of any one of claims 21, 22, 30, 31 and 48 to 53, the Raf inhibitor for use of any one of claims 23 to 25, 30, 31 and 53, the Raf inhibitor for use of any one of claims 26, 30, 31 and 53, the inhibitor for use of any one of claims 26, 31, 39, 52 and 53, the inhibitor for use of any one of claims 26, 30, 31, 52 and 53, the MEK inhibitor for use of any one of claims 3 to 31, 30, 31, and 53, the MEK inhibitor for use of any one of claims 3 to 52, 30, 52 and 53, the inhibitor for use of any one of claims 3 to 52, 30 to 52, and 53, the medium, the inhibitor for use of any one of claims 3 to 52, and 52, the inhibitor for use of any one of claims 3 to 52, and 53, the inhibitor for at least one of the treatment of the cycle, and the treatment of any one of claims 3 to 52, 3 to 52, and 53, and the inhibitor for use of the PI inhibitor for use of any one of claims, and 52 is at least one of the inhibitors.
55. The method of claim 54, the TEAD inhibitor of claim 54, the cMET inhibitor of claim 54, the KRAS G12/G13 inhibitor of claim 54, the SHP2 inhibitor of claim 54, the MEK inhibitor of claim 54, the ERK inhibitor of claim 54, the Raf inhibitor of claim 54, the EGFR inhibitor of claim 54, the PI3K inhibitor of claim 54, the MDM2 inhibitor of claim 54, or the CDK4/6 inhibitor of claim 54, wherein the daily dose of the TEAD inhibitor is from 15mg to 100mg per day of administration.
56. The method of claim 55, the TEAD inhibitor of claim 55, the cMET inhibitor of claim 55, the KRAS G12/G13 inhibitor of claim 55, the SHP2 inhibitor of claim 54, the MEK inhibitor of claim 55, the ERK inhibitor of claim 55, the Raf inhibitor of claim 55, the EGFR inhibitor of claim 55, the PI3K inhibitor of claim 55, the MDM2 inhibitor of claim 55, or the 4/6 inhibitor of claim 55, wherein the daily dose of the TEAD inhibitor at each administration day is 15mg, 30mg, 45mg, 60mg, 75mg, 90mg, or 100mg.
CN202280057427.8A 2021-09-01 2022-08-30 Pharmaceutical combinations comprising TEAD inhibitors and their use for cancer treatment Pending CN117835978A (en)

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US63/366,829 2022-06-22
PCT/IB2022/058104 WO2023031781A1 (en) 2021-09-01 2022-08-30 Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers

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