Small-Molecule BET Inhibitors in Clinical and Preclinical Development and Their Therapeutic Potential

被引：28
|
作者：
Yu, Lei [1 ,2 ]
Wang, Zhen [1 ,2 ]
Zhang, Zhang [1 ]
Ren, Xiaomei [1 ]
Lu, Xiaoyun [1 ]
Ding, Ke [1 ]
机构：
[1] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou 510530, Guangdong, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
来源：
CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2015年 / 15卷 / 08期
关键词：
Acetyl-lysine (KAc) binding pocket; Bromodomain (BRDs); Bromo and extra-terminal (BET) proteins; Medicinal implications; Selectivity; Small-molecule inhibitors; NF-KAPPA-B; BROMODOMAIN PROTEIN BRD4; FRAGMENT-BASED DISCOVERY; SELECTIVE-INHIBITION; P-TEFB; HIV LATENCY; CHROMATIN; TRANSCRIPTION; BINDING; FAMILY;
D O I：
10.2174/1568026615666150302110135
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Lysine acetylation is a pivotal mechanism in chromatin processes and the regulation of gene transcription. The acetylated lysine residues of histones are exclusively recognized by bromodomains (BRDs) known as epigenetic reader. Proteins containing BRDs undergo a post-translational modification (PTM) with development of cellular signaling and disease biology. The bromo and extra-terminal (BET) proteins are the second subfamily, which play important roles in cellular proliferation, cell cycle progression and chromatin compaction. Recently, a variety of small molecules have been reported to interact with the BET family proteins and accelerate the validation of BET proteins as druggable targets for treatment of cancers, inflammation and related diseases. In this review, we will summarize the small-molecule inhibitors in clinical and preclinical studies of the BET family bromodomains and their medicinal implications.
引用
收藏
页码：776 / 794
页数：19
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