Structure-Activity Relationship Study of N6-Benzoyladenine-Type BRD4 Inhibitors and Their Effects on Cell Differentiation and TNF-α Production

被引：10

作者：

Amemiya, Seika ^{[1
]}

Yamaguchi, Takao ^{[1
]}

Sakai, Taki ^{[1
]}

Hashimoto, Yuichi ^{[1
]}

Noguchi-Yachide, Tomomi ^{[1
]}

机构：

[1] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2016年 / 64卷 / 09期

关键词：

bromodomain; bromodomain and extra-terminal domain (BET); BRD4; cell differentiation; tumor necrosis factor (TNF)-alpha; BROMODOMAIN PROTEIN BRD4; NF-KAPPA-B; P-TEFB; C-MYC; LEUKEMIA; RECOGNITION; THALIDOMIDE; RELEASE; TARGET;

D O I：

10.1248/cpb.c16-00410

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Bromodomains are epigenetic 'readers' of histone acetylation. The first potent bromodomain and extra terminal domain (BET) inhibitors, (+)-JQ1 and I-BET762 (also known as GSK525762), were reported in 2010. Some BET inhibitors are already under clinical trial for the treatment of cancers, but so far, only a few chemical scaffolds are available. We have reported potent N-6-benzoyladenine-based inhibitors of BRD4, a BET family member that serves as a key mediator of transcriptional elongation. Here we present an analysis of the structure activity relationships of these inhibitors. Among the compounds examined, 20, 28 and 29 enhanced all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation and inhibited tumor necrosis factor (TNF)-alpha production by THP-1 cells.

引用

页码：1378 / 1383

页数：6

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