HUE031976T2 - Human form of histone methyl transferase inhibitor EZH2 - Google Patents
Human form of histone methyl transferase inhibitor EZH2 Download PDFInfo
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- HUE031976T2 HUE031976T2 HUE13774979A HUE13774979A HUE031976T2 HU E031976 T2 HUE031976 T2 HU E031976T2 HU E13774979 A HUE13774979 A HU E13774979A HU E13774979 A HUE13774979 A HU E13774979A HU E031976 T2 HUE031976 T2 HU E031976T2
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Classifications
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- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
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| HUE19180479A HUE060881T2 (hu) | 2012-04-13 | 2013-04-11 | Sóforma az EZH2 gátláshoz |
| HUE16191716A HUE045353T2 (hu) | 2012-04-13 | 2013-04-11 | N-((4,6-dimetil-2-oxo-1,2-dihidropiridin-3-il)-metil)-5-(etil-(tetrahidro-2H-pirán-4-il) -amino)-4-metil-4'-(morfolino-metil)-[1,1'-bifenil]-3-karboxamid-hidrobromid a hematológiai rendszer egy sejtszaporodásos rendellenességének kezelésében való alkalmazásra |
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| HUE16191716A HUE045353T2 (hu) | 2012-04-13 | 2013-04-11 | N-((4,6-dimetil-2-oxo-1,2-dihidropiridin-3-il)-metil)-5-(etil-(tetrahidro-2H-pirán-4-il) -amino)-4-metil-4'-(morfolino-metil)-[1,1'-bifenil]-3-karboxamid-hidrobromid a hematológiai rendszer egy sejtszaporodásos rendellenességének kezelésében való alkalmazásra |
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| WO2013075084A1 (en) | 2011-11-18 | 2013-05-23 | Constellation Pharmaceuticals | Modulators of methyl modifying enzymes, compositions and uses thereof |
| CA2862289C (en) | 2012-02-10 | 2019-11-26 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| BR112014025508B1 (pt) | 2012-04-13 | 2020-11-17 | Eisai R&D Management Co., Ltd. | forma de sal de um inibidor de histona metiltransferase ezh2 humana |
| MX367793B (es) | 2012-04-13 | 2019-09-06 | Epizyme Inc | Terapia de combinación para tratar cáncer. |
| US9562041B2 (en) | 2012-05-16 | 2017-02-07 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| JP6461803B2 (ja) | 2012-10-15 | 2019-01-30 | エピザイム，インコーポレイティド | 置換ベンゼン化合物 |
| US9688665B2 (en) * | 2012-10-15 | 2017-06-27 | Epizyme, Inc. | Methods of treating cancer |
| WO2014151142A1 (en) | 2013-03-15 | 2014-09-25 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| NZ630205A (en) | 2013-04-30 | 2017-03-31 | Glaxosmithkline Intellectual Property (No 2) Ltd | Enhancer of zeste homolog 2 inhibitors |
| ES2640386T3 (es) | 2013-07-10 | 2017-11-02 | Glaxosmithkline Intellectual Property (No. 2) Limited | Potenciador de inhibidores del homólogo Zeste 2 |
| WO2015023915A1 (en) | 2013-08-15 | 2015-02-19 | Constellation Pharmaceuticals, Inc. | Indole derivatives as modulators of methyl modifying enzymes, compositions and uses thereof |
| EA038869B1 (ru) | 2013-10-16 | 2021-10-29 | Эпизим, Инк. | Кристаллические формы гидрохлорида n-((4,6-диметил-2-оксо-1,2-дигидропиридин-3-ил)метил)-5-(этил(тетрагидро-2h-пиран-4-ил)амино)-4-метил-4'-(морфолинометил)-[1,1'-бифенил]-3-карбоксамида, фармацевтические композиции на их основе и способы их применения |
| JP2016533364A (ja) * | 2013-10-18 | 2016-10-27 | エピザイム，インコーポレイティド | 癌を処置する方法 |
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| ES2863996T3 (es) | 2013-12-06 | 2021-10-13 | Epizyme Inc | Terapia de combinación para el tratamiento del cáncer |
| LT3157527T (lt) | 2014-06-17 | 2023-07-25 | Epizyme, Inc. | Ezh2 inhibitoriai, skirti limfomos gydymui |
| ES2725928T3 (es) | 2014-06-20 | 2019-09-30 | Constellation Pharmaceuticals Inc | Formas cristalinas de 2-((4S)-6-(4-clorofenil)-1-metil-4H-benzo[c]isoxazolo[4,5-e]azepin-4-il)acetamida |
| IL289947B2 (en) | 2014-10-16 | 2024-06-01 | Epizyme Inc | Method for treating cancer |
| US10786511B2 (en) | 2014-11-17 | 2020-09-29 | Epizyme, Inc. | Method for treating cancer |
| AR102767A1 (es) | 2014-12-05 | 2017-03-22 | Lilly Co Eli | Inhibidores de ezh2 |
| WO2016172199A1 (en) | 2015-04-20 | 2016-10-27 | Epizyme, Inc. | Combination therapy for treating cancer |
| WO2016201328A1 (en) | 2015-06-10 | 2016-12-15 | Epizyme, Inc. | Ezh2 inhibitors for treating lymphoma |
| SG10201909199PA (en) | 2015-08-24 | 2019-11-28 | Epizyme Inc | Method for treating cancer |
| TW201718598A (zh) | 2015-08-27 | 2017-06-01 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| WO2017040190A1 (en) | 2015-08-28 | 2017-03-09 | Constellation Pharmaceuticals, Inc. | Crystalline forms of (r)-n-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1h-indole-3-carboxamide |
| CA3011186A1 (en) | 2016-01-29 | 2017-08-03 | Epizyme, Inc. | Combination therapy for treating cancer |
| WO2017210395A1 (en) * | 2016-06-01 | 2017-12-07 | Epizyme, Inc. | Use of ezh2 inhibitors for treating cancer |
| MA45406A (fr) | 2016-06-17 | 2019-04-24 | Epizyme Inc | Inhibiteurs d'ezh2 pour traiter le cancer |
| US10457640B2 (en) | 2016-10-19 | 2019-10-29 | Constellation Pharmaceuticals, Inc. | Synthesis of inhibitors of EZH2 |
| WO2018137639A1 (zh) * | 2017-01-25 | 2018-08-02 | 恩瑞生物医药科技（上海）有限公司 | 一种组蛋白甲基转移酶ezh2抑制剂、其制备方法及其医药用途 |
| US11642346B2 (en) | 2017-03-31 | 2023-05-09 | Epizyme, Inc. | Combination therapy for treating cancer |
| US11602529B2 (en) | 2017-06-02 | 2023-03-14 | Epizyme, Inc. | Use of EZH2 inhibitors for treating cancer |
| EP3678663A4 (en) | 2017-09-05 | 2021-06-02 | Epizyme, Inc. | POLYTHERAPY FOR CANCER TREATMENT |
| CN112399857A (zh) | 2018-07-09 | 2021-02-23 | 盲人庇护基金会 | Prc2亚单位的抑制治疗眼失调 |
| EP4003532B1 (en) | 2019-07-24 | 2024-09-04 | Constellation Pharmaceuticals, Inc. | Crystalline forms of 7-chloro-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-2,4-dimethyl-n-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide |
| KR20220066892A (ko) | 2019-08-22 | 2022-05-24 | 주노 쎄러퓨티크스 인코퍼레이티드 | Ｔ 세포 요법 및 제스트 동족체 2의 인핸서 (ｅｚｈ2) 억제제의 병용 요법 및 관련 방법 |
| BR112022012258A2 (pt) * | 2019-12-20 | 2022-08-30 | Epizyme Inc | Sal cristalino de bromidreto de um inibidor de ezh2, sua preparação e composição farmacêutica útil para o tratamento de câncer |
| WO2022208552A1 (en) * | 2021-03-31 | 2022-10-06 | Msn Laboratories Private Limited, R&D Center | Crystalline forms of [1,1'-Biphenyl]-3-carboxamide, N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-5-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-4-methyl-4'-(4-morpholinylmethyl)-, hydrobromide (1:1) and process for its preparation thereof |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0733729A (ja) | 1993-07-26 | 1995-02-03 | Kirin Brewery Co Ltd | Ｎ−シアノ−ｎ′−置換−アリールカルボキシイミダミド化合物の製造法 |
| HUT74450A (en) | 1993-12-27 | 1996-12-30 | Eisai Co Ltd | Anthranilic acid derivative and pharmaceutical compns. contg. such compds. |
| DE19516776A1 (de) | 1995-05-10 | 1996-11-14 | Boehringer Ingelheim Int | Chromatin-Regulatorgene |
| US5741819A (en) | 1995-06-07 | 1998-04-21 | 3-Dimensional Pharmaceuticals, Inc. | Arylsulfonylaminobenzene derivatives and the use thereof as factor Xa inhibitors |
| JP3906935B2 (ja) | 1995-12-18 | 2007-04-18 | 杏林製薬株式会社 | Ｎ−置換ジオキソチアゾリジルベンズアミド誘導体及びその製造法 |
| JP2002525352A (ja) | 1998-09-30 | 2002-08-13 | ザ、プロクター、エンド、ギャンブル、カンパニー | ２−置換ケトアミド |
| UA71587C2 (uk) | 1998-11-10 | 2004-12-15 | Шерінг Акцієнгезелльшафт | Аміди антранілової кислоти та їхнє застосування як лікарських засобів |
| US6710058B2 (en) | 2000-11-06 | 2004-03-23 | Bristol-Myers Squibb Pharma Company | Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors |
| KR100828982B1 (ko) | 2000-12-28 | 2008-05-14 | 시오노기세이야쿠가부시키가이샤 | 칸나비노이드 2형 수용체 친화 작용을 갖는 피리돈 유도체 |
| US7700293B2 (en) | 2001-08-02 | 2010-04-20 | The Regents Of The University Of Michigan | Expression profile of prostate cancer |
| TW200303304A (en) * | 2002-02-18 | 2003-09-01 | Astrazeneca Ab | Chemical compounds |
| DE60329981D1 (de) | 2002-02-19 | 2009-12-24 | Shionogi & Co | Antipruriginosa |
| TW200306155A (en) | 2002-03-19 | 2003-11-16 | Du Pont | Benzamides and advantageous compositions thereof for use as fungicides |
| US7442685B2 (en) | 2003-06-13 | 2008-10-28 | The University Of North Carolina At Chapel Hill | DOT1 histone methyltransferases as a target for identifying therapeutic agents for leukemia |
| CN1989131A (zh) * | 2004-03-30 | 2007-06-27 | 希龙公司 | 取代的噻吩衍生物用作抗癌药 |
| DE602005017781D1 (de) | 2004-06-01 | 2009-12-31 | Univ North Carolina | Rekonstituierter histon-methyltransferase-komplex und verfahren zur identifizierung von modulatoren dafür |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| US7923219B2 (en) | 2005-06-02 | 2011-04-12 | The University Of North Carolina At Chapel Hill | Ubiquitin E3 ligase |
| FR2889526B1 (fr) | 2005-08-04 | 2012-02-17 | Aventis Pharma Sa | 7-aza-indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
| US8710233B2 (en) | 2005-10-19 | 2014-04-29 | Gruenenthal Gmbh | Vanilloid receptor ligands and use thereof for the production of pharmaceutical preparations |
| ATE510822T1 (de) | 2005-10-21 | 2011-06-15 | Merck Sharp & Dohme | Kaliumkanalinhibitoren |
| US20090203057A1 (en) | 2005-10-28 | 2009-08-13 | Yi Zhang | Protein demethylases comprising a jmjc domain |
| WO2007070818A1 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| EP2730661A1 (en) | 2006-01-20 | 2014-05-14 | The University of North Carolina at Chapel Hill | Diagnostic and therapeutic targets for leukemia |
| EP2018166A2 (en) | 2006-05-15 | 2009-01-28 | Irm Llc | Terephthalamate compounds and compositions, and their use as hiv integrase inhibitors |
| WO2007136592A2 (en) | 2006-05-18 | 2007-11-29 | Amphora Discovery Corporation | 2-0x0-l,2-dihydr0quin0line derivatives, compositions, and uses thereof as antiproliferative agents |
| WO2008108825A2 (en) | 2006-10-10 | 2008-09-12 | Burnham Institute For Medical Research | Neuroprotective compositions and methods |
| MX2009008531A (es) | 2007-02-16 | 2009-08-26 | Amgen Inc | Cetonas de heterociclilo que contienen nitrogeno y su uso como inhibidores de c-met. |
| EP2137158A4 (en) | 2007-02-28 | 2012-04-18 | Methylgene Inc | LOW-MOLECULAR INHIBITORS OF PROTEINARGININE METHYLTRANSFERASES (PRMTS) |
| WO2008113006A1 (en) | 2007-03-14 | 2008-09-18 | Xenon Pharmaceuticals Inc. | Methods of using quinolinone compounds in treating sodium channel-mediated diseases or conditions |
| DE102007017884A1 (de) | 2007-04-13 | 2008-10-16 | Grünethal GmbH | Neue Vanilloid-Rezeptor Liganden und ihre Verwendung zur Herstellung von Arzneimitteln |
| WO2009006577A2 (en) | 2007-07-03 | 2009-01-08 | The Regents Of The University Of Michigan | Compositions and methods for inhibiting ezh2 |
| DE102007047737A1 (de) * | 2007-10-05 | 2009-04-30 | Merck Patent Gmbh | Piperidin- und Piperazinderivate |
| WO2009058298A1 (en) | 2007-10-31 | 2009-05-07 | Merck & Co., Inc. | P2x3, receptor antagonists for treatment of pain |
| BRPI0821227A2 (pt) | 2007-12-19 | 2015-06-16 | Cancer Rec Tech Ltd | Composto, composição farmacêutica, método para preparar a mesma, uso de um composto, método para tratar uma doença ou distúrbio, para inibir função de raf e para inibir proliferação celular, inibir progressão do ciclo celular, promover apoptose, ou uma combinação de um ou mais dos mesmos |
| WO2009124137A2 (en) | 2008-04-01 | 2009-10-08 | Mount Sinai School Of Medicine Of New York University | Method of suppressing gene transcription through histone lysine methylation |
| US20100113415A1 (en) | 2008-05-29 | 2010-05-06 | Rajapakse Hemaka A | Epha4 rtk inhibitors for treatment of neurological and neurodegenerative disorders and cancer |
| AU2009279616A1 (en) | 2008-08-08 | 2010-02-11 | New York Blood Center | Small molecule inhibitors of retroviral assembly and maturation |
| FR2934995B1 (fr) | 2008-08-14 | 2010-08-27 | Sanofi Aventis | Composes d'azetidines polysubstitues, leur preparation et leur application en therapeutique |
| EP2411007A4 (en) | 2009-03-27 | 2012-12-05 | Uab Research Foundation | MODULATION OF IRES-MEDIATED TRANSLATION |
| US20110021362A1 (en) | 2009-07-20 | 2011-01-27 | Constellation Pharmaceuticals | Agents for stimulating activity of methyl modifying enzymes and methods of use thereof |
| US8329149B2 (en) | 2009-12-30 | 2012-12-11 | Avon Products, Inc. | Topical lightening composition and uses thereof |
| EP2566328B1 (en) * | 2010-05-07 | 2015-03-04 | GlaxoSmithKline LLC | Indazoles |
| ES2528269T3 (es) * | 2010-05-07 | 2015-02-06 | Glaxosmithkline Llc | Azaindazoles |
| EP2566327B1 (en) | 2010-05-07 | 2017-03-29 | Glaxosmithkline LLC | Indoles |
| AU2011298987B2 (en) | 2010-09-10 | 2017-09-28 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| US20130310379A1 (en) | 2010-11-19 | 2013-11-21 | Constellation Pharmaceuticals | Modulators of methyl modifying enzymes, compositions and uses thereof |
| JP5908493B2 (ja) | 2010-12-01 | 2016-04-26 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーＧｌａｘｏＳｍｉｔｈＫｌｉｎｅ ＬＬＣ | インドール |
| RU2013130253A (ru) | 2010-12-03 | 2015-01-10 | Эпизайм, Инк. | 7-деазапуриновые регуляторы метилтрансферазы гистонов и способы их применения |
| EP2681216B1 (en) | 2011-02-28 | 2017-09-27 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| TWI598336B (zh) | 2011-04-13 | 2017-09-11 | 雅酶股份有限公司 | 經取代之苯化合物 |
| ES2718900T3 (es) | 2012-03-12 | 2019-07-05 | Epizyme Inc | Inhibidores de EZH2 humana y métodos de uso de los mismos |
| MX367793B (es) | 2012-04-13 | 2019-09-06 | Epizyme Inc | Terapia de combinación para tratar cáncer. |
| BR112014025508B1 (pt) | 2012-04-13 | 2020-11-17 | Eisai R&D Management Co., Ltd. | forma de sal de um inibidor de histona metiltransferase ezh2 humana |
| US9562041B2 (en) | 2012-05-16 | 2017-02-07 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| US9688665B2 (en) | 2012-10-15 | 2017-06-27 | Epizyme, Inc. | Methods of treating cancer |
| EA038869B1 (ru) | 2013-10-16 | 2021-10-29 | Эпизим, Инк. | Кристаллические формы гидрохлорида n-((4,6-диметил-2-оксо-1,2-дигидропиридин-3-ил)метил)-5-(этил(тетрагидро-2h-пиран-4-ил)амино)-4-метил-4'-(морфолинометил)-[1,1'-бифенил]-3-карбоксамида, фармацевтические композиции на их основе и способы их применения |
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