公开(公告)号：EP3087080A1

公开(公告)日：2016-11-02

申请号：EP14827687.6

申请日：2014-12-24

Applicant: President and Fellows of Harvard College

Inventor： SHAIR, Matthew, D. ,  RAMHARTER, Juergen ,  PELISH, Henry, Efrem ,  LIAU, Brian, Bor-Jen ,  AHN, Jae Young

IPC: C07D493/08 ,  C07D493/22 ,  C07D519/00 ,  C07K14/575 ,  C07K16/26

CPC classification number: C07D493/08 ,  C07D493/22 ,  C07D519/00 ,  C07K14/575 ,  C07K16/26

Abstract: Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the □-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

Abstract translation: 式（A），（B），（C），（D）和（E）的化合物被认为可用作治疗各种各样的病症的治疗剂，例如包括但不限于与血管生成相关的病症 CDK8和/或CDK19激酶活性。 还提供了抑制CDK8和/或CDK19激酶活性的方法，调节β-连环蛋白途径的方法，调节STAT1活性的方法，调节TGFβ/ BMP途径的方法，调节细胞中HIF-1-α活性的方法 以及使用式（A），（B），（C），（D）或（E）的化合物增加BIM表达以诱导细胞凋亡的方法。 进一步提供CDK8和CDK19点突变体及其使用方法。

公开(公告)号：EP3087080B1

公开(公告)日：2018-11-28

申请号：EP14827687.6

申请日：2014-12-24

Applicant: President and Fellows of Harvard College

Inventor： SHAIR, Matthew, D. ,  RAMHARTER, Juergen ,  PELISH, Henry, Efrem ,  LIAU, Brian, Bor-Jen ,  AHN, Jae Young

IPC: C07D493/08 ,  C07D493/22 ,  C07D519/00 ,  C07K14/575 ,  C07K16/26

CPC classification number: C07D493/08 ,  C07D493/22 ,  C07D519/00 ,  C07K14/575 ,  C07K16/26

Abstract: Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the -catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.