CA2990835A1 - Compositions and methods for treating cancer - Google Patents
Compositions and methods for treating cancer Download PDFInfo
- Publication number
- CA2990835A1 CA2990835A1 CA2990835A CA2990835A CA2990835A1 CA 2990835 A1 CA2990835 A1 CA 2990835A1 CA 2990835 A CA2990835 A CA 2990835A CA 2990835 A CA2990835 A CA 2990835A CA 2990835 A1 CA2990835 A1 CA 2990835A1
- Authority
- CA
- Canada
- Prior art keywords
- pp2a
- inhibitor
- kinase inhibitor
- protein kinase
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 141
- 201000011510 cancer Diseases 0.000 title claims abstract description 75
- 238000000034 method Methods 0.000 title claims abstract description 55
- 239000000203 mixture Substances 0.000 title description 31
- 239000012190 activator Substances 0.000 claims abstract description 82
- 229940043355 kinase inhibitor Drugs 0.000 claims abstract description 67
- 239000003909 protein kinase inhibitor Substances 0.000 claims abstract description 59
- 101000741929 Caenorhabditis elegans Serine/threonine-protein phosphatase 2A catalytic subunit Proteins 0.000 claims abstract 13
- 150000001875 compounds Chemical class 0.000 claims description 57
- -1 Jak2 inhibitor Substances 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 24
- 239000003112 inhibitor Substances 0.000 claims description 18
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims description 16
- 239000002067 L01XE06 - Dasatinib Substances 0.000 claims description 16
- 229960002448 dasatinib Drugs 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 150000003384 small molecules Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 12
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 claims description 11
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
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- 229910052736 halogen Inorganic materials 0.000 claims description 8
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- BOIPLTNGIAPDBY-UHFFFAOYSA-N 2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine Chemical compound C1=CC(Cl)=CC=C1OCCCCCCN=C(NC#N)NC1=CC=NC=C1 BOIPLTNGIAPDBY-UHFFFAOYSA-N 0.000 claims description 5
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
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- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
- MHFUWOIXNMZFIW-WNQIDUERSA-N (2s)-2-hydroxypropanoic acid;n-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide Chemical compound C[C@H](O)C(O)=O.C1CN(C)CCN1C1=CC(NC2=NNC(C)=C2)=NC(SC=2C=CC(NC(=O)C3CC3)=CC=2)=N1 MHFUWOIXNMZFIW-WNQIDUERSA-N 0.000 claims description 4
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
- SYYBDNPGDKKJDU-ZDUSSCGKSA-N 1-[5-bromo-4-methyl-2-[[(2S)-2-morpholinyl]methoxy]phenyl]-3-(5-methyl-2-pyrazinyl)urea Chemical compound C1=NC(C)=CN=C1NC(=O)NC1=CC(Br)=C(C)C=C1OC[C@H]1OCCNC1 SYYBDNPGDKKJDU-ZDUSSCGKSA-N 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 4
- PSPFQEBFYXJZEV-UHFFFAOYSA-N N'-(1,8-dimethyl-4-imidazo[1,2-a]quinoxalinyl)ethane-1,2-diamine Chemical compound C1=C(C)C=C2N3C(C)=CN=C3C(NCCN)=NC2=C1 PSPFQEBFYXJZEV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- PMJIHLSCWIDGMD-UHFFFAOYSA-N tideglusib Chemical compound O=C1SN(C=2C3=CC=CC=C3C=CC=2)C(=O)N1CC1=CC=CC=C1 PMJIHLSCWIDGMD-UHFFFAOYSA-N 0.000 claims description 4
- 101000777293 Homo sapiens Serine/threonine-protein kinase Chk1 Proteins 0.000 claims description 3
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 3
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 3
- 102100031081 Serine/threonine-protein kinase Chk1 Human genes 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 230000002357 endometrial effect Effects 0.000 claims description 3
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 3
- 229960004066 trametinib Drugs 0.000 claims description 3
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical group CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 2
- FAYAUAZLLLJJGH-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[5-[2-(4-thieno[3,2-d]pyrimidinylamino)ethyl]-2-thiazolyl]urea Chemical compound ClC1=CC=CC(NC(=O)NC=2SC(CCNC=3C=4SC=CC=4N=CN=3)=CN=2)=C1 FAYAUAZLLLJJGH-UHFFFAOYSA-N 0.000 claims description 2
- GZGLPBNOIFLLRE-UHFFFAOYSA-N 1-[(5-methoxy-2-thiophen-2-ylquinazolin-4-yl)amino]-3-methylpyrrole-2,5-dione Chemical compound C=12C(OC)=CC=CC2=NC(C=2SC=CC=2)=NC=1NN1C(=O)C=C(C)C1=O GZGLPBNOIFLLRE-UHFFFAOYSA-N 0.000 claims description 2
- JCSGFHVFHSKIJH-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-4-(1-methyl-3-indolyl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C1=CC=C(Cl)C=C1Cl JCSGFHVFHSKIJH-UHFFFAOYSA-N 0.000 claims description 2
- MOVBBVMDHIRCTG-LJQANCHMSA-N 4-[(3s)-1-azabicyclo[2.2.2]oct-3-ylamino]-3-(1h-benzimidazol-2-yl)-6-chloroquinolin-2(1h)-one Chemical compound C([N@](CC1)C2)C[C@@H]1[C@@H]2NC1=C(C=2NC3=CC=CC=C3N=2)C(=O)NC2=CC=C(Cl)C=C21 MOVBBVMDHIRCTG-LJQANCHMSA-N 0.000 claims description 2
- KDKUVYLMPJIGKA-UHFFFAOYSA-N 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide Chemical compound N=1N(C(=O)C=2C(=CC=CC=2F)F)C(N)=NC=1NC1=CC=C(S(N)(=O)=O)C=C1 KDKUVYLMPJIGKA-UHFFFAOYSA-N 0.000 claims description 2
- HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 claims description 2
- ZLHFILGSQDJULK-UHFFFAOYSA-N 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3C4=CC=C(Cl)C=C4C(=NCC3=CN=2)C=2C(=CC=CC=2F)OC)=C1 ZLHFILGSQDJULK-UHFFFAOYSA-N 0.000 claims description 2
- GBJVVSCPOBPEIT-UHFFFAOYSA-N AZT-1152 Chemical compound N=1C=NC2=CC(OCCCN(CC)CCOP(O)(O)=O)=CC=C2C=1NC(=NN1)C=C1CC(=O)NC1=CC=CC(F)=C1 GBJVVSCPOBPEIT-UHFFFAOYSA-N 0.000 claims description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims description 2
- 229940125497 HER2 kinase inhibitor Drugs 0.000 claims description 2
- 239000002145 L01XE14 - Bosutinib Substances 0.000 claims description 2
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 claims description 2
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 claims description 2
- JZRMBDHPALEPDM-UHFFFAOYSA-N N-(6-Chloro-9H-pyrido[3,4-b]indol-8-yl)-3-pyridinecarboxamide Chemical compound C=12NC3=CN=CC=C3C2=CC(Cl)=CC=1NC(=O)C1=CC=CN=C1 JZRMBDHPALEPDM-UHFFFAOYSA-N 0.000 claims description 2
- XKFTZKGMDDZMJI-HSZRJFAPSA-N N-[5-[(2R)-2-methoxy-1-oxo-2-phenylethyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methyl-1-piperazinyl)benzamide Chemical compound O=C([C@H](OC)C=1C=CC=CC=1)N(CC=12)CC=1NN=C2NC(=O)C(C=C1)=CC=C1N1CCN(C)CC1 XKFTZKGMDDZMJI-HSZRJFAPSA-N 0.000 claims description 2
- JOOXLOJCABQBSG-UHFFFAOYSA-N N-tert-butyl-3-[[5-methyl-2-[4-[2-(1-pyrrolidinyl)ethoxy]anilino]-4-pyrimidinyl]amino]benzenesulfonamide Chemical compound N1=C(NC=2C=C(C=CC=2)S(=O)(=O)NC(C)(C)C)C(C)=CN=C1NC(C=C1)=CC=C1OCCN1CCCC1 JOOXLOJCABQBSG-UHFFFAOYSA-N 0.000 claims description 2
- PQCXVIPXISBFPN-UHFFFAOYSA-N SB 415286 Chemical compound C1=C(Cl)C(O)=CC=C1NC1=C(C=2C(=CC=CC=2)[N+]([O-])=O)C(=O)NC1=O PQCXVIPXISBFPN-UHFFFAOYSA-N 0.000 claims description 2
- 101710164184 Synaptic vesicular amine transporter Proteins 0.000 claims description 2
- 102100034333 Synaptic vesicular amine transporter Human genes 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 229950000971 baricitinib Drugs 0.000 claims description 2
- XUZMWHLSFXCVMG-UHFFFAOYSA-N baricitinib Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2C=3C=CNC=3N=CN=2)=C1 XUZMWHLSFXCVMG-UHFFFAOYSA-N 0.000 claims description 2
- 229960003736 bosutinib Drugs 0.000 claims description 2
- UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 claims description 2
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- OBWNXGOQPLDDPS-UHFFFAOYSA-N n-(2,6-diethylphenyl)-3-[[4-(4-methylpiperazin-1-yl)benzoyl]amino]-4,6-dihydro-1h-pyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound CCC1=CC=CC(CC)=C1NC(=O)N1CC(C(NC(=O)C=2C=CC(=CC=2)N2CCN(C)CC2)=NN2)=C2C1 OBWNXGOQPLDDPS-UHFFFAOYSA-N 0.000 claims description 2
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| PCT/US2016/039022 WO2016210134A1 (en) | 2015-06-23 | 2016-06-23 | Compositions and methods for treating cancer |
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| US12441707B2 (en) | 2019-12-30 | 2025-10-14 | Tyra Biosciences, Inc. | Indazole compounds |
| WO2021188949A1 (en) * | 2020-03-20 | 2021-09-23 | Atux Iskay Llc | 3-diarylmethylenes and uses thereof |
| WO2021202780A2 (en) * | 2020-04-01 | 2021-10-07 | Engine Biosciences Pte. Ltd. | Methods and compositions for treating cancer |
| WO2022094615A1 (en) * | 2020-10-29 | 2022-05-05 | The Regents Of The University Of California | Compounds and methods for increased antisense activity |
| CN114617969B (zh) * | 2020-12-14 | 2023-08-25 | 上海市肿瘤研究所 | 乐伐替尼和Aurora-A激酶抑制剂在制备抑制癌症的药物中的应用 |
| JP2024508687A (ja) * | 2021-02-08 | 2024-02-28 | ラプタ セラピューティクス オーワイ | プロテインホスファターゼ２ａ（ｐｐ２ａ）の置換環状調節物質およびこれを用いた方法 |
| CN112816453B (zh) * | 2021-02-09 | 2022-07-08 | 黑龙江大学 | 蛋白在预测药物性能上的应用 |
| CN113616795B (zh) * | 2021-08-31 | 2023-06-20 | 上海交通大学医学院附属瑞金医院 | Pp2a激动剂防治由正常衰老或pp2a活性或表达降低所导致的精神障碍 |
| CN114984221A (zh) * | 2022-05-25 | 2022-09-02 | 浙江大学 | Pp2a及其激活剂在急性缺血性脑卒中制药、标记的应用 |
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| US20090020197A1 (en) * | 2007-07-16 | 2009-01-22 | Key Safety Systems, Inc. | Gas generating compositions and airbag inflators |
| WO2009114703A2 (en) * | 2008-03-12 | 2009-09-17 | Fox Chase Cancer Center | Combination therapy for the treatment of cancer |
| WO2009117769A1 (en) * | 2008-03-25 | 2009-10-01 | Newcastle Innovation Limited | Inhibition of c-kit cancers |
| WO2010120711A1 (en) * | 2009-04-13 | 2010-10-21 | The Ohio State University Research Foundation | Protein phosphatase 2a-activating agents |
| US9134297B2 (en) * | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
| HK1198384A1 (en) * | 2011-08-16 | 2015-04-17 | Mt. Sinai School Of Medicine | Tricyclic compounds as anticancer agents |
| JP2015500885A (ja) * | 2011-12-22 | 2015-01-08 | スレッショルド ファーマシューティカルズ，インコーポレイテッド | 癌を治療するためのｃｈｋ１阻害剤と組み合わせた低酸素活性化プロドラッグの投与 |
| US20140357573A1 (en) * | 2013-03-15 | 2014-12-04 | Life Technologies Corporation | Prognostic assay for squamous cell lung carcinoma |
| WO2015138496A1 (en) | 2014-03-11 | 2015-09-17 | Icahn School Of Medicine At Mount Sinai | Constrained tricyclic sulfonamides |
| US9937186B2 (en) | 2014-03-11 | 2018-04-10 | Icahn School Of Medicine At Mount Sinai | Sulfonamides derived from tricyclyl-2-aminocycloalkanols as anticancer agents |
-
2016
- 2016-06-23 EP EP16815302.1A patent/EP3313819A1/en not_active Withdrawn
- 2016-06-23 CN CN201680044840.5A patent/CN108779073A/zh active Pending
- 2016-06-23 CA CA2990835A patent/CA2990835A1/en not_active Abandoned
- 2016-06-23 JP JP2017567214A patent/JP2018518522A/ja active Pending
- 2016-06-23 WO PCT/US2016/039022 patent/WO2016210134A1/en not_active Ceased
- 2016-06-23 US US15/738,870 patent/US10744141B2/en active Active
- 2016-06-23 AU AU2016281646A patent/AU2016281646A1/en not_active Abandoned
-
2017
- 2017-12-24 IL IL256523A patent/IL256523A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US10744141B2 (en) | 2020-08-18 |
| CN108779073A (zh) | 2018-11-09 |
| JP2018518522A (ja) | 2018-07-12 |
| IL256523A (en) | 2018-02-28 |
| US20180185382A1 (en) | 2018-07-05 |
| AU2016281646A1 (en) | 2018-02-01 |
| EP3313819A1 (en) | 2018-05-02 |
| WO2016210134A1 (en) | 2016-12-29 |
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