WO2024106879A1 - Composition pharmaceutique pour la prévention ou le traitement du cancer, comprenant un inhibiteur d'ezh2 et un inhibiteur de btk - Google Patents

Composition pharmaceutique pour la prévention ou le traitement du cancer, comprenant un inhibiteur d'ezh2 et un inhibiteur de btk Download PDF

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WO2024106879A1
WO2024106879A1 PCT/KR2023/018176 KR2023018176W WO2024106879A1 WO 2024106879 A1 WO2024106879 A1 WO 2024106879A1 KR 2023018176 W KR2023018176 W KR 2023018176W WO 2024106879 A1 WO2024106879 A1 WO 2024106879A1
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cancer
pharmaceutical composition
lymphoma
inhibitor
ezh2
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PCT/KR2023/018176
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Korean (ko)
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임정연
정유림
김세빈
김라은
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인제대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • This invention was made under the support of the Ministry of Science and ICT through project identification number 1711172425 and task number 2022R1F1A1061005.
  • the research management agency for the project is the National Research Foundation of Korea, the research project name is "Individual Basic Research (Ministry of Science and ICT)", and the research project is Myung-eun: "Development of a combination immunotherapy using PROTAC-based epigenetic control factor EZH2 targeting drug and immune checkpoint inhibitor for the treatment of refractory lymphoma", the project carrying out institution is Inje University, and the research period is 2022.06.01 ⁇ 2023.02.28.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of cancer containing an EZH2 inhibitor and a BTK inhibitor, which treats not only Epstein-Barr virus (EBV)-related lymphoma, which has had a low therapeutic effect so far, but also other cancer types. It was confirmed that the effect was significantly excellent.
  • EBV Epstein-Barr virus
  • Lymphoma is a blood cancer that occurs when B or T lymphocytes become cancerous. Lymphoma can develop in lymph nodes, spleen, bone marrow, blood, or other organs and eventually become cancer. Lymphoma is a malignant tumor that occurs in lymphoid tissue and can occur in areas other than lymphoid tissue. Cases that occur in areas other than lymphoid tissue are called extranodal lymphomas, and are known to occur mainly in areas where the nose and throat are connected, the gastrointestinal tract, and the brain. Lymphoma accounts for 2.1% of all cancers in the United States, 2.8% in the United Kingdom, and 4% in Korea, making it a common cancer in the East.
  • Lymphoma is largely divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma. According to WHO statistics, as of 2020, there are 627,439 new cases of lymphoma, of which the incidence rates of Hodgkin's lymphoma and non-Hodgkin's lymphoma are 13% and 87%, respectively.
  • Epstein-Barr virus a herpes virus, infects more than 90% of normal people and causes asymptomatic latent infection in most people, but the immune system is weakened after bone marrow transplant or organ transplant. In individuals with long-term decline, EBV is known to cause tumors such as lymphoproliferative disease, Burkitt's lymphoma, Nasopharyngeal carcinoma (NPC), and Hodgkin's disease. there is.
  • Lymphocytic diseases associated with EBV include Hodgkin's lymphoma, nasal type extranodal NK-T cell lymphoma, and post-transplant lymphoproliferative disease (PTLD).
  • PTLD post-transplant lymphoproliferative disease
  • EBV-related tumors such as Burkitt's lymphoma
  • existing treatments for EBV-related tumors include reduction of immunosuppressants, use of antiviral drugs, chemotherapy, and administration of rituximab antibody, but treatment response rate is low. Due to differences in treatment, an effective treatment has not yet been established. Therefore, there is currently an urgent need to develop new treatments for the treatment and cure of EBV-related tumors.
  • the bones in our body maintain the body's shape, enable exercise, and are involved in calcium regulation.
  • a tissue called bone marrow, which is less dense than bone, where white blood cells, red blood cells, platelets, etc. It functions to create blood cells.
  • Leukemia is a cancer that occurs in these blood cells, and is a general term for blood cancer in which abnormal blood cells (mostly derived from white blood cells, but rarely also from the erythroid and platelet systems) proliferate excessively, suppressing the production of normal white blood cells, red blood cells, and platelets. am.
  • a decrease in the normal number of white blood cells can cause a decrease in immunity and cause sepsis due to bacterial infection.
  • a decrease in red blood cells causes symptoms of anemia (dizziness, headache, difficulty breathing), and a decrease in platelets causes bleeding tendencies. Additionally, the overproliferated leukemia cells themselves can cause high fever, fatigue, bone pain, diarrhea, decreased consciousness, difficulty breathing, and bleeding tendencies.
  • Leukemia is divided into acute and chronic depending on the degree of cell differentiation, that is, the rate of deterioration, and is divided into myeloid and lymphocytic depending on the origin of the cell. It is commonly classified into four types: Acute myeloid leukemia, Acute lymphocytic leukemia, Chronic myeloid leukemia, and Chronic lymphocytic leukemia.
  • the large intestine is divided into the appendix, cecum, colon, rectum, and anal canal.
  • the colon is further divided into the ascending colon, transverse colon, descending colon, and sigmoid colon.
  • Colon cancer is a malignant tumor that occurs in the appendix, colon, and rectum. Depending on where it occurs, it is called colon cancer if it occurs in the colon, and rectal cancer if it occurs in the rectum. These are collectively called colon cancer or colorectal cancer.
  • breast cancer is a malignant tumor that can spread outside the breast and threaten life.
  • cells in the breast can turn into cancerous cells, so there are quite a few types of breast cancer that can occur.
  • Breast cancer is the most common cancer among women in developed countries such as the United States and Europe, and is the leading cause of death for American women between the ages of 40 and 55. Breast cancer develops in one in nine women during her lifetime, and the number of breast cancer patients is also increasing by about 15% every year. In Korea, breast cancer accounted for approximately 11.9% of female cancer patients in 1995, becoming the third most common cancer after cervical cancer and stomach cancer, and the fifth highest mortality rate after stomach cancer, liver cancer, uterine cancer, and lung cancer. There is a trend of increasing every year.
  • EZH2 (Enhancer of zeste homolog 2) is a histone-lysine N-methyltransferase enzyme encoded by the EZH2 gene that participates in histone methylation and ultimately transcriptional repression. EZH2 levels are abnormally elevated in cancer tissues compared to normal tissues, and EZH2 is most highly expressed in late-stage tumors or poor prognosis. EZH2 can slow tumor growth by suppressing genes that suppress tumor development or blocking EZH2 activity.
  • BTK (Bruton's tyrosine kinase) is a member of the tyrosine kinase subfamily and belongs to the Tec family of kinases. It is mainly expressed in B cells and is distributed throughout the lymphatic, hematopoietic, and hematological systems.
  • the B cell receptor (BCR) promotes proliferation and survival in chronic lymphocytic leukemia (CLL) and various lymphomas, including non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL). plays a decisive role in regulating.
  • CLL chronic lymphocytic leukemia
  • NHL non-Hodgkin lymphoma
  • MCL mantle cell lymphoma
  • DLBCL diffuse large B-cell lymphoma
  • BTK Bruton's tyrosine kinase
  • the present inventors used a PROTAC (Proteolysis targeting chimera)-based EZH2 inhibitor and a BTK inhibitor in combination to demonstrate a therapeutic effect not only on Epstein-Barr virus (EBV)-related lymphoma, which has had a low therapeutic effect so far, but also on other cancer types. After confirming that it was excellent, the present invention was completed.
  • PROTAC Proteolysis targeting chimera
  • BTK BTK inhibitor
  • An object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer, comprising an EZH2 inhibitor and a BTK inhibitor.
  • Another object of the present invention is to provide a use of a pharmaceutical composition comprising an EZH2 inhibitor and a BTK inhibitor for treating cancer.
  • Another object of the present invention is to provide a method of treating cancer by combined administration of an EZH2 inhibitor and a BTK inhibitor.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of cancer containing an EZH2 inhibitor and a BTK inhibitor, which treats not only Epstein-Barr virus (EBV)-related lymphoma, which has had a low therapeutic effect so far, but also other cancer types. It was confirmed that the effect was significantly excellent.
  • EBV Epstein-Barr virus
  • One example of the present invention relates to a pharmaceutical composition for preventing or treating cancer, comprising an EZH2 inhibitor and a BTK inhibitor.
  • the EZH2 inhibitor may be based on PROTAC (Proteolysis targeting chimera).
  • PROTAC is a heterobifunctional small molecule composed of two active domains and a linker, and has the ability to remove specific unwanted proteins by inducing intracellular protein degradation.
  • PROTAC-based EZH2 inhibitor may refer to a substance aimed at decomposing EZH2 protein.
  • the EZH2 inhibitor may be MS1943 or MS177, but is not limited thereto.
  • the EZH2 inhibitor may be a compound having the structure of Structural Formula 1 (MS1943) or Structural Formula 2 (MS177) below, but is not limited thereto.
  • the BTK inhibitor may be one or more selected from the group consisting of ibrutinib, acalabrutinib, and zanubrutinib, but is not limited thereto.
  • cancer includes lymphoma, leukemia, colon cancer, breast cancer, pancreatic cancer, lung cancer, stomach cancer, brain cancer, uterine cancer, ovarian cancer, prostate cancer, testicular cancer, bladder cancer, esophageal cancer, liver cancer, gallbladder cancer, sarcoma, skin cancer, multiple myeloma, thyroid cancer, and It may be selected from the group consisting of head and neck cancer, but is not limited thereto.
  • the lymphoma may be a refractory lymphoma.
  • the lymphoma may be Epstein-Barr virus (EBV)-related lymphoma.
  • EBV Epstein-Barr virus
  • lymphoma includes lymphoproliferative disease, Burkitt's lymphoma, Nasopharyngeal carcinoma (NPC), Hodgkin's disease, and diffuse large B-cell lymphoma. It may be one or more types selected from the group consisting of B cell lymphoma.
  • the EZH2 inhibitor and the BTK inhibitor may exist as separate agents, but are not limited thereto.
  • the EZH2 inhibitor and the BTK inhibitor may be administered simultaneously, sequentially, or alternately.
  • the EZH2 inhibitor and the BTK inhibitor are administered for about 1 minute, about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, about 45 minutes, about 1 hour, about 2 hours, about 4 hours, about 6 hours, About 12 hours, about 24 hours, about 48 hours, about 72 hours, about 96 hours, about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 8 weeks, or about It may be administered sequentially at a time interval of 12 weeks, but is not limited to this.
  • the EZH2 inhibitor is used in an amount of 0.1 mg/kg to 1000 mg/kg, 0.1 mg/kg to 500 mg/kg, 0.1 mg/kg to 100 mg/kg, 0.1 mg/kg to 50 mg/kg, 1 mg/kg. kg to 1000 mg/kg, 1 mg/kg to 500 mg/kg, 1 mg/kg to 100 mg/kg, 1 mg/kg to 50 mg/kg, 5 mg/kg to 1000 mg/kg, 5 mg/kg It may be administered at a dose of kg to 500 mg/kg, 5 mg/kg to 100 mg/kg, or 5 mg/kg to 50 mg/kg, but is not limited thereto.
  • the BTK inhibitor is 0.1 mg/kg to 1000 mg/kg, 0.1 mg/kg to 500 mg/kg, 0.1 mg/kg to 100 mg/kg, 0.1 mg/kg to 50 mg/kg, 1 mg/kg. kg to 1000 mg/kg, 1 mg/kg to 500 mg/kg, 1 mg/kg to 100 mg/kg, 1 mg/kg to 50 mg/kg, 5 mg/kg to 1000 mg/kg, 5 mg/kg It may be administered at a dose of kg to 500 mg/kg, 5 mg/kg to 100 mg/kg, or 5 mg/kg to 50 mg/kg, but is not limited thereto.
  • the pharmaceutical composition may be administered 1 to 6 times, 1 to 5 times, 1 to 4 times, or 1 to 3 times daily, if necessary, but is not limited thereto.
  • the pharmaceutical composition of the present invention can be administered in the following ways: oral, buccal, inhalation spray, sublingual, rectal, transdermal, vaginal mucosal, transmucosal, topical, nasal, or enteral administration; Parenteral administration, such as intramuscular injection, subcutaneous injection, intramedullary injection, as well as intrathecal or direct cerebral administration, in situ administration, subcutaneous, intraperitoneal, intravenous injection, intraarticular synovial, intrasternal, intrahepatic, intralesional, Intracranial, intraperitoneal, nasal, or intraocular injection; or other methods of drug delivery.
  • Parenteral administration such as intramuscular injection, subcutaneous injection, intramedullary injection, as well as intrathecal or direct cerebral administration, in situ administration, subcutaneous, intraperitoneal, intravenous injection, intraarticular synovial, intrasternal, intrahepatic, intralesional, Intracranial, intraperitoneal, nasal, or intraocular injection; or other methods of drug delivery.
  • the pharmaceutical composition may further include a pharmaceutically acceptable carrier, diluent, or excipient.
  • carriers commonly used in preparation include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, and polyvinyl. It may be one or more selected from the group consisting of pyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but is not limited thereto. .
  • the diluent may be one or more selected from the group consisting of dicalcium phosphate, calcium sulfate, lactose, sorbitol, sucrose, inositol, cellulose, kaolin, mannitol, sodium chloride, dried starch, and powdered sugar, but is limited thereto. It doesn't work.
  • the excipient is one or more selected from the group consisting of anti-adhesion agents, binders, coating agents, colorants, dyes, disintegrants, flavoring agents, lubricants, lubricants, preservatives, adsorbents, sweeteners, vehicles, wetting agents, emulsifiers, and pH buffering agents. It may be, but is not limited to this.
  • the pharmaceutical composition may be in the form of tablets, capsules, granules, syrups, powders, lozenges, cachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, ointments, creams, and injections. , but is not limited to this.
  • treatment refers to reducing, alleviating, or improving the symptoms of a disease or condition, improving symptoms due to metabolic potential, suppressing the disease or symptoms, such as preventing the progression of the disease or disorder, improving the disease or condition, It means causing regression of a disease or condition, alleviating the condition caused by the disease or condition, or preventing symptoms of the disease or condition.
  • the term "about” means ⁇ 10%, more preferably ⁇ 5%, and most preferably ⁇ 2% of the value it modifies, so those skilled in the art will be able to determine the range of the term “about” according to the modified value. can be decided clearly.
  • Another example of the present invention relates to the use of a pharmaceutical composition containing an EZH2 inhibitor and a BTK inhibitor for treating cancer.
  • Another example of the present invention relates to a method of treating cancer comprising administering an effective amount of an EZH2 inhibitor and a BTK inhibitor to a subject in need of treatment.
  • subject is meant to include humans (e.g., patients) and animals (e.g., mice, rats, dogs, cats, rabbits, chickens, monkeys, etc.).
  • animals e.g., mice, rats, dogs, cats, rabbits, chickens, monkeys, etc.
  • the term “effective amount” means an amount (e.g., dose) of a pharmaceutical composition that provides a significant reduction in the clinical symptoms of the disease or condition being treated without causing excessive toxic side effects.
  • dose refers to the weight (e.g., milligrams (mg)) of active agent per kilogram (kg) of a subject's body weight.
  • the EZH2 inhibitor and the BTK inhibitor may exist as separate agents, but are not limited thereto.
  • the EZH2 inhibitor and the BTK inhibitor may be administered simultaneously, sequentially, or alternately.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of cancer containing an EZH2 inhibitor and a BTK inhibitor, which treats not only Epstein-Barr virus (EBV)-related lymphoma, which has had a low therapeutic effect so far, but also other cancer types. It was confirmed that the effect was significantly excellent.
  • EBV Epstein-Barr virus
  • Figure 1 is a graph showing the results of measuring absorbance when a B-cell lymphoma cell line (Daudi) was treated with an EZH2 inhibitor or a BTK inhibitor alone, and when an EZH2 inhibitor and a BTK inhibitor were combined.
  • Daudi B-cell lymphoma cell line
  • Figure 2 is a graph showing the results of measuring absorbance when a T-cell leukemia cell line (Jurkat) was treated with an EZH2 inhibitor or a BTK inhibitor alone, and when an EZH2 inhibitor and a BTK inhibitor were combined.
  • Figure 3 is a graph showing the results of measuring absorbance when a colon cancer cell line (HCT-116) was treated with an EZH2 inhibitor or a BTK inhibitor alone, and when an EZH2 inhibitor and a BTK inhibitor were combined.
  • Figure 4 is a graph showing the results of measuring absorbance when a breast cancer cell line (MDA-MB-231) was treated with an EZH2 inhibitor or a BTK inhibitor alone, and when an EZH2 inhibitor and a BTK inhibitor were combined.
  • the present invention relates to a pharmaceutical composition for preventing or treating cancer, comprising an EZH2 inhibitor and a BTK inhibitor.
  • B-cell lymphoma cell line (Daudi), T-cell leukemia cell line (Jurkat), colon cancer cell line (HCT-116), and breast cancer cell line (MDA-MB-231).
  • Cells were cultured in RPMI medium (Gibco) supplemented with 10% FBS (Gibco), antibiotics (Gibco), and glutamax (Gibco).
  • BTK inhibitor Ibrutinib
  • PROTAC-based EZH2 inhibitor MS1943, MS177
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of cancer containing an EZH2 inhibitor and a BTK inhibitor, which treats not only Epstein-Barr virus (EBV)-related lymphoma, which has had a low therapeutic effect so far, but also other cancer types. It was confirmed that the effect was significantly excellent.
  • EBV Epstein-Barr virus

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Abstract

La présente invention concerne une composition pharmaceutique pour la prévention ou le traitement du cancer, comprenant un inhibiteur d'EZH2 et un inhibiteur de BTK. Il a été confirmée que la composition pharmaceutique présenterun effet thérapeutique sensiblement élevé dans le traitement de lymphomes associés au virus d'Epstein-Barr (EBV) pour lesquels il y a une faible efficacité thérapeutique jusqu'à présent, et d'autres cancers également.
PCT/KR2023/018176 2022-11-17 2023-11-13 Composition pharmaceutique pour la prévention ou le traitement du cancer, comprenant un inhibiteur d'ezh2 et un inhibiteur de btk WO2024106879A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200007851A (ko) * 2017-05-18 2020-01-22 지앙수 헨그루이 메디슨 컴퍼니 리미티드 종양 치료용 약물의 제조에 있어서의 ezh2 억제제 및 btk 억제제의 조합물의 용도
US20200078362A1 (en) * 2016-12-02 2020-03-12 Epizyme, Inc. Combination therapy for treating cancer
US20200093815A1 (en) * 2015-07-28 2020-03-26 Constellation Pharmaceuticals, Inc. Combinations of ezh2 inhibitors with further agents for use in the treatment of cancer
KR20210117347A (ko) * 2013-12-06 2021-09-28 에피자임, 인코포레이티드 암 치료를 위한 병용 요법

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KR20210117347A (ko) * 2013-12-06 2021-09-28 에피자임, 인코포레이티드 암 치료를 위한 병용 요법
US20200093815A1 (en) * 2015-07-28 2020-03-26 Constellation Pharmaceuticals, Inc. Combinations of ezh2 inhibitors with further agents for use in the treatment of cancer
US20200078362A1 (en) * 2016-12-02 2020-03-12 Epizyme, Inc. Combination therapy for treating cancer
KR20200007851A (ko) * 2017-05-18 2020-01-22 지앙수 헨그루이 메디슨 컴퍼니 리미티드 종양 치료용 약물의 제조에 있어서의 ezh2 억제제 및 btk 억제제의 조합물의 용도

Non-Patent Citations (1)

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Title
MA ANQI; STRATIKOPOULOS ELIAS; PARK KWANG-SU; WEI JIELI; MARTIN TIPHAINE C.; YANG XIAOBAO; SCHWARZ MEGAN; LESHCHENKO VIOLETTA; RIA: "Discovery of a first-in-class EZH2 selective degrader", NATURE CHEMICAL BIOLOGY, NATURE PUBLISHING GROUP US, NEW YORK, vol. 16, no. 2, 9 December 2019 (2019-12-09), New York, pages 214 - 222, XP036996008, ISSN: 1552-4450, DOI: 10.1038/s41589-019-0421-4 *

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