JP2015511603A5 - - Google Patents
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- JP2015511603A5 JP2015511603A5 JP2015500523A JP2015500523A JP2015511603A5 JP 2015511603 A5 JP2015511603 A5 JP 2015511603A5 JP 2015500523 A JP2015500523 A JP 2015500523A JP 2015500523 A JP2015500523 A JP 2015500523A JP 2015511603 A5 JP2015511603 A5 JP 2015511603A5
- Authority
- JP
- Japan
- Prior art keywords
- seq
- amino acid
- wild type
- substitution
- acid position
- 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.)
- Granted
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- 235000001014 amino acid Nutrition 0.000 claims description 44
- 150000001413 amino acids Chemical group 0.000 claims description 44
- 238000006467 substitution reaction Methods 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 26
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 claims description 22
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 claims description 22
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 20
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 20
- 230000035772 mutation Effects 0.000 claims description 15
- 239000003112 inhibitor Substances 0.000 claims description 10
- 239000004475 Arginine Substances 0.000 claims description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 8
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 8
- 206010025323 Lymphomas Diseases 0.000 claims description 8
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 8
- 235000004279 alanine Nutrition 0.000 claims description 8
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 235000018417 cysteine Nutrition 0.000 claims description 8
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 8
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 8
- 239000004474 valine Substances 0.000 claims description 8
- 208000006994 Precancerous Conditions Diseases 0.000 claims description 7
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 4
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
- 208000007541 Preleukemia Diseases 0.000 claims description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 4
- 235000009582 asparagine Nutrition 0.000 claims description 4
- 229960001230 asparagine Drugs 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 4
- 201000003444 follicular lymphoma Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 229930182817 methionine Natural products 0.000 claims description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
- 229920001184 polypeptide Polymers 0.000 claims description 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 239000000758 substrate Substances 0.000 claims description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 2
- 150000007523 nucleic acids Chemical group 0.000 claims description 2
- 230000009257 reactivity Effects 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 238000002203 pretreatment Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13/418,242 US9175331B2 (en) | 2010-09-10 | 2012-03-12 | Inhibitors of human EZH2, and methods of use thereof |
| US13/418,242 | 2012-03-12 | ||
| PCT/US2013/030565 WO2013138361A1 (en) | 2012-03-12 | 2013-03-12 | Inhibitors of human ezh2, and methods of use thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017245743A Division JP6592071B2 (ja) | 2012-03-12 | 2017-12-22 | ヒトｅｚｈ２の阻害剤およびその使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015511603A JP2015511603A (ja) | 2015-04-20 |
| JP2015511603A5 true JP2015511603A5 (enExample) | 2016-05-12 |
| JP6321619B2 JP6321619B2 (ja) | 2018-05-09 |
Family
ID=47913638
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015500523A Active JP6321619B2 (ja) | 2012-03-12 | 2013-03-12 | ヒトｅｚｈ２の阻害剤およびその使用方法 |
| JP2017245743A Active JP6592071B2 (ja) | 2012-03-12 | 2017-12-22 | ヒトｅｚｈ２の阻害剤およびその使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017245743A Active JP6592071B2 (ja) | 2012-03-12 | 2017-12-22 | ヒトｅｚｈ２の阻害剤およびその使用方法 |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP2825161B1 (enExample) |
| JP (2) | JP6321619B2 (enExample) |
| KR (4) | KR102453519B1 (enExample) |
| CN (2) | CN110420327B (enExample) |
| AU (4) | AU2013232229B2 (enExample) |
| CA (2) | CA2867282C (enExample) |
| DK (1) | DK2825161T3 (enExample) |
| ES (1) | ES2718900T3 (enExample) |
| HU (1) | HUE042271T2 (enExample) |
| PL (1) | PL2825161T3 (enExample) |
| PT (1) | PT2825161T (enExample) |
| RU (2) | RU2704445C2 (enExample) |
| TR (1) | TR201904660T4 (enExample) |
| WO (1) | WO2013138361A1 (enExample) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2841142C (en) | 2010-06-23 | 2020-12-15 | Ryan D. Morin | Biomarkers for non-hodgkin lymphomas and uses thereof |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| EP2780013A4 (en) | 2011-11-18 | 2015-07-01 | Constellation Pharmaceuticals Inc | MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF |
| US9085583B2 (en) | 2012-02-10 | 2015-07-21 | Constellation—Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| CN104768555B (zh) | 2012-04-13 | 2018-10-30 | Epizyme股份有限公司 | 用于治疗癌症的联合治疗 |
| PL3628670T3 (pl) | 2012-04-13 | 2023-02-20 | Epizyme, Inc. | Postać soli dla inhibicji ezh2 |
| WO2014049488A1 (en) * | 2012-09-28 | 2014-04-03 | Pfizer Inc. | Benzamide and heterobenzamide compounds |
| SG10201705989YA (en) | 2012-10-15 | 2017-08-30 | Epizyme Inc | Substituted benzene compounds |
| MX376008B (es) * | 2012-10-15 | 2025-03-07 | Epizyme Inc | Inhibidor de ezh2 para usarse en el tratamiento de sarcoma epiteloide. |
| EP2970305B1 (en) | 2013-03-15 | 2017-02-22 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| WO2015023915A1 (en) | 2013-08-15 | 2015-02-19 | Constellation Pharmaceuticals, Inc. | Indole derivatives as modulators of methyl modifying enzymes, compositions and uses thereof |
| SI3057962T1 (sl) | 2013-10-16 | 2024-01-31 | Epizyme, Inc. | Oblika hidrokloridne soli za ezh2 inhibicijo |
| AU2014337121A1 (en) * | 2013-10-18 | 2016-04-14 | Epizyme, Inc. | Method of treating cancer |
| KR20220165809A (ko) | 2013-12-06 | 2022-12-15 | 에피자임, 인코포레이티드 | 암 치료를 위한 병용 요법 |
| US20160361309A1 (en) * | 2014-02-26 | 2016-12-15 | Glaxosmithkline Intellectual Property (No.2) Limited | Methods of treating cancer patients responding to ezh2 inhibitor gsk126 |
| PL3157527T3 (pl) * | 2014-06-17 | 2023-08-07 | Epizyme, Inc. | Inhibitory ezh2 do leczenia chłoniaka |
| MX384423B (es) | 2014-06-19 | 2025-03-14 | Memorial Sloan Kettering Cancer Center | Biomarcadores para la respuesta a inhibidores del mejorador del homólogo 2 de zeste (ezh2). |
| CA2963149A1 (en) * | 2014-10-16 | 2016-04-21 | Epizyme, Inc. | Method for treating cancer |
| WO2016073956A1 (en) | 2014-11-06 | 2016-05-12 | Dana-Farber Cancer Institute, Inc. | Ezh2 inhibitors and uses thereof |
| HUE062159T2 (hu) * | 2014-11-17 | 2023-10-28 | Epizyme Inc | Módszer a rák kezelésére N-((4,6-dimetil-2-oxo-l,2-dihidropiridin-3-il)metil)-5-(etil(tetrahidro-2H -pirán-4-il)amino)-4-metil-4'-(morfolinmetil)-[1,1'-bifenil]-3-karboxamiddal |
| ES2722048T3 (es) | 2014-12-23 | 2019-08-07 | Novartis Ag | Compuestos de triazolopirimidina y usos de los mismos |
| WO2016172332A1 (en) * | 2015-04-22 | 2016-10-27 | The University Of North Carolina At Chapel Hill | A novel compound for the treatment of ewing sarcoma and high-throughput assays for identifying small molecules that modulate aberrant chromatin accessibility |
| JP6890097B2 (ja) | 2015-06-10 | 2021-06-18 | エピザイム，インコーポレイティド | リンパ腫を処置するためのｅｚｈ２阻害剤 |
| MX2018002344A (es) | 2015-08-24 | 2018-07-06 | Epizyme Inc | Metodo para tratar el cancer. |
| TW201718598A (zh) | 2015-08-27 | 2017-06-01 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| US10577350B2 (en) | 2015-08-28 | 2020-03-03 | 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 |
| AU2016325643B2 (en) * | 2015-09-25 | 2022-07-21 | Epizyme, Inc. | Method of treating malignant rhabdoid tumor or small cell cancer of the ovary of the hypercalcemic type |
| US20180321256A1 (en) | 2015-11-05 | 2018-11-08 | Epizyme, Inc. | Flow cytometry for monitoring histone h3 methylation status |
| CN109069508A (zh) * | 2016-04-22 | 2018-12-21 | 达纳-法伯癌症研究所股份有限公司 | Ezh2抑制剂及其用途 |
| WO2017201585A1 (en) * | 2016-05-26 | 2017-11-30 | Genea Ip Holdings Pty Ltd | Modulators of dux4 for regulation of muscle function |
| CA3025933A1 (en) | 2016-06-01 | 2017-12-07 | Epizyme, Inc. | Use of ezh2 inhibitors for treating cancer |
| JP2019521988A (ja) | 2016-06-17 | 2019-08-08 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤 |
| US11091489B2 (en) | 2016-06-20 | 2021-08-17 | Novartis Ag | Crystalline forms of a triazolopyrimidine compound |
| EP3472166A1 (en) | 2016-06-20 | 2019-04-24 | Novartis AG | Imidazopyrimidine compounds useful for the treatment of cancer |
| EP3472161B1 (en) | 2016-06-20 | 2020-03-25 | Novartis AG | Triazolopyridine compounds and uses thereof |
| WO2018075598A1 (en) | 2016-10-19 | 2018-04-26 | Constellation Pharmaceuticals, Inc. | Synthesis of inhibitors of ezh2 |
| CA3044691A1 (en) | 2016-10-26 | 2018-05-03 | Genea Biocells USA (Holdings), Inc. | Improved generation of muscle lineage cells and therapeutic uses thereof |
| WO2018086592A1 (zh) * | 2016-11-11 | 2018-05-17 | 上海海雁医药科技有限公司 | 4,5,6-三取代吲唑类衍生物、其制法与医药上的用途 |
| CN106963765B (zh) * | 2017-03-28 | 2020-04-07 | 上海交通大学医学院附属第九人民医院 | Ezh2抑制剂化合物在制备治疗眼部黑色素瘤的药物中的应用 |
| US11642346B2 (en) | 2017-03-31 | 2023-05-09 | Epizyme, Inc. | Combination therapy for treating cancer |
| JP2020522687A (ja) | 2017-06-02 | 2020-07-30 | エピザイム，インコーポレイティド | 癌を処置するためのｅｚｈ２阻害剤の使用 |
| KR102758037B1 (ko) | 2017-08-18 | 2025-01-22 | 코테라 바이오사이언스 인코포레이티드 | Tg02의 다형성 형태 |
| EP3678663A4 (en) | 2017-09-05 | 2021-06-02 | Epizyme, Inc. | POLYTHERAPY FOR CANCER TREATMENT |
| WO2019204998A1 (zh) * | 2018-04-25 | 2019-10-31 | 北京肿瘤医院 | Ezh2抑制剂在治疗粘膜型黑色素瘤中的应用 |
| KR102810863B1 (ko) * | 2018-06-03 | 2025-05-20 | 엑셀시오 파마테크 랩스 | 비-밀집 심근증 치료 방법 |
| EP3831822A4 (en) | 2018-07-27 | 2022-03-23 | Suzhou Sinovent Pharmaceuticals Co., Ltd. | POLYSUBSTITUTED BENZENE COMPOUND AND METHOD FOR PREPARING IT AND ITS USE |
| WO2020219606A1 (en) | 2019-04-22 | 2020-10-29 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Use of erk5 inhibitors for treating gliomas in pediatric subjects |
| CN110960525A (zh) * | 2019-11-26 | 2020-04-07 | 济南大学 | 新型eed-ezh2相互作用抑制剂的确定和评价 |
| CN113024516B (zh) * | 2021-03-29 | 2022-05-17 | 中国药科大学 | 双靶点parp/ezh2抑制剂、制备方法及用途 |
| US20240350508A1 (en) | 2021-08-25 | 2024-10-24 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of ezh2 inhibitors for the treatment of aortic valve stenosis |
| 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 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of 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 |
| CN119143880A (zh) * | 2024-09-20 | 2024-12-17 | 上海交通大学医学院附属第九人民医院 | 抗ezh2蛋白抗体及其应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5763263A (en) | 1995-11-27 | 1998-06-09 | Dehlinger; Peter J. | Method and apparatus for producing position addressable combinatorial libraries |
| US7700293B2 (en) | 2001-08-02 | 2010-04-20 | The Regents Of The University Of Michigan | Expression profile of prostate cancer |
| US7563589B2 (en) | 2004-06-01 | 2009-07-21 | The University Of North Carolina At Chapel Hill | Reconstituted histone methyltransferase complex and methods of identifying modulators thereof |
| ES2324435B1 (es) * | 2005-10-27 | 2010-05-31 | Fundacion Para El Estudio De La Hematologia Y Hemoterapia De Aragon (Fehha) | Procedimiento y dispositivo de analisis in vitro de mrna de genes implicados en neoplasias hematologicas. |
| WO2008101118A2 (en) * | 2007-02-14 | 2008-08-21 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | A gene expression signature identifying pro-angiogenic genes in ovarian tumor endothelial cell isolates |
| WO2009006577A2 (en) * | 2007-07-03 | 2009-01-08 | The Regents Of The University Of Michigan | Compositions and methods for inhibiting ezh2 |
| 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 |
| US8637509B2 (en) | 2010-05-07 | 2014-01-28 | Glaxosmithkline Llc | Azaindazoles |
| EP2566327B1 (en) | 2010-05-07 | 2017-03-29 | Glaxosmithkline LLC | Indoles |
| WO2011140325A1 (en) | 2010-05-07 | 2011-11-10 | Glaxosmithkline Llc | Indazoles |
| PL2614369T3 (pl) * | 2010-09-10 | 2016-08-31 | Epizyme Inc | Sposób określania przydatności inhibitorów ludzkiego ezh2 w leczeniu |
| JO3438B1 (ar) * | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| BR112014007603A2 (pt) * | 2011-09-30 | 2017-06-13 | Glaxosmithkline Llc | métodos de tratamento do câncer |
-
2013
- 2013-03-12 EP EP13711265.2A patent/EP2825161B1/en active Active
- 2013-03-12 KR KR1020217018417A patent/KR102453519B1/ko active Active
- 2013-03-12 JP JP2015500523A patent/JP6321619B2/ja active Active
- 2013-03-12 CN CN201910052279.0A patent/CN110420327B/zh active Active
- 2013-03-12 CA CA2867282A patent/CA2867282C/en active Active
- 2013-03-12 AU AU2013232229A patent/AU2013232229B2/en not_active Ceased
- 2013-03-12 ES ES13711265T patent/ES2718900T3/es active Active
- 2013-03-12 KR KR1020147028560A patent/KR102267502B1/ko active Active
- 2013-03-12 RU RU2014141045A patent/RU2704445C2/ru active
- 2013-03-12 KR KR1020237033924A patent/KR20230145531A/ko not_active Ceased
- 2013-03-12 HU HUE13711265A patent/HUE042271T2/hu unknown
- 2013-03-12 WO PCT/US2013/030565 patent/WO2013138361A1/en not_active Ceased
- 2013-03-12 PL PL13711265T patent/PL2825161T3/pl unknown
- 2013-03-12 CN CN201380024734.7A patent/CN104540500B/zh active Active
- 2013-03-12 PT PT13711265T patent/PT2825161T/pt unknown
- 2013-03-12 EP EP18214827.0A patent/EP3536314A1/en not_active Withdrawn
- 2013-03-12 CA CA3177515A patent/CA3177515A1/en active Pending
- 2013-03-12 TR TR2019/04660T patent/TR201904660T4/tr unknown
- 2013-03-12 RU RU2019132222A patent/RU2019132222A/ru unknown
- 2013-03-12 KR KR1020227034498A patent/KR102587175B1/ko active Active
- 2013-03-12 DK DK13711265.2T patent/DK2825161T3/en active
-
2017
- 2017-12-22 JP JP2017245743A patent/JP6592071B2/ja active Active
-
2018
- 2018-02-19 AU AU2018201176A patent/AU2018201176A1/en not_active Abandoned
-
2019
- 2019-10-17 AU AU2019250181A patent/AU2019250181A1/en not_active Abandoned
-
2021
- 2021-04-07 AU AU2021202119A patent/AU2021202119A1/en not_active Abandoned
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