公开(公告)号：US20170119780A1

公开(公告)日：2017-05-04

申请号：US15346677

申请日：2016-11-08

Applicant: Epizyme, Inc.

Inventor： Kevin Wayne Kuntz ,  Richard Chesworth ,  Kenneth William Duncan ,  Heike Keilhack ,  Natalie Warholic ,  Christine Klaus ,  Sarah Kathleen Knutson ,  Timothy James Nelson Wigle ,  Masashi Seki ,  Syuji Shirotori ,  Satoshi Kawano

IPC: A61K31/5377 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4439 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/551 ,  A61K31/553 ,  A61K31/506 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/4412 ,  A61K31/496

CPC classification number: A61K31/5377 ,  A61K31/4412 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  A61K31/553 ,  C07D213/64 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D491/08 ,  C07D491/107 ,  C07D498/08

Abstract: The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

公开(公告)号：US20170065600A1

公开(公告)日：2017-03-09

申请号：US15132610

申请日：2016-04-19

Applicant: EPIZYME, INC.

Inventor： Kevin Wayne Kuntz ,  Sarah Kathleen Knutson ,  Timothy James Nelson Wigle ,  Robert A. Copeland ,  Victoria M. Richon ,  Margaret D. Scott ,  Christopher J. Sneeringer ,  Roy M. Pollock

IPC: A61K31/5377 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/551 ,  G01N33/50 ,  A61K31/4439 ,  A61K31/4427 ,  A61K31/496 ,  A61K31/497 ,  A61K31/7076 ,  A61K31/4412

CPC classification number: A61K31/5377 ,  A61K31/4412 ,  A61K31/4427 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/551 ,  A61K31/7076 ,  A61K31/711 ,  A61K38/17 ,  C07D405/12 ,  C07D473/34 ,  C12Q1/48 ,  C12Q1/68 ,  G01N33/5011 ,  G01N33/57426 ,  G01N2333/91011 ,  G01N2333/91017 ,  G01N2800/52 ,  Y10T436/143333

Abstract: The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

Abstract translation: 本发明涉及抑制人组蛋白甲基转移酶EZH2的野生型和某些突变体形式，其是催化组蛋白H3（H3-K27）上赖氨酸27的单通三甲基化的PRC2复合物的催化亚单位。 在一个实施方案中，抑制对于EZH2的突变体形式是选择性的，使得与某些癌症相关的H3-K27的三甲基化被抑制。 该方法可用于治疗包括滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤（DLBCL）的癌症。 还提供了用于鉴定EZH2的突变形式的小分子选择性抑制剂的方法以及用于测定受试者中对EZH2抑制剂的反应性的方法。