bromodomains：表观遗传医学新靶点及其抑制剂.pdf

PROGRESS IN PHARMACEUTICAL SCIENCES 2016,40 8 :619-626 ( ) 619 Bromodomains：表观遗传医学新靶点及其抑制剂 周啸峰，焦宇，张智敏，唐伟方 * （中国药科大学理学院，江苏 南京 211198） [ 摘要 ] Bromodomains（BRDs）是一类能够特异性识别乙酰化赖氨酸残基的保守蛋白结构域，存在于染色质及与转录相关的蛋白 中，其功能包括染色质重塑和转录调控，并在细胞内由乙酰化介导的蛋白-蛋白相互作用中发挥极为重要的作用，是多种疾病（包括癌 症、炎症和自身免疫病）的表观遗传医学靶点。介绍 BRDs 的生物学功能、结构及分类，主要从 BET bromodomain 抑制剂和非 BET bromodomain 抑制剂两个方面对 BRDs 抑制剂的研究进展作一综述，为高活性和选择性的 BRDs 抑制剂研发提供参考。 [ 关键词 ] bromodomain；乙酰化作用；赖氨酸残基；染色质；转录调控；抑制剂 [ 中图分类号 ] R394 [ 文献标志码 ] A [ 文章编号 ] 1001-5094（2016）08-0619-08 Bromodomains: Promising New Targets in Emerging Epigenetic Medicine and Their Inhibitors ZHOU Xiaofeng, JIAO Yu, ZHANG Zhimin, TANG Weifang (School of Science, China Pharmaceutical University, Nanjing 211198, China) [Abstract] Bromodomains(BRDs) are a type of conserved protein domains that are found in chromatin and transcription-associated proteins and able to recognize and bind to acetylated lysine residue. They are involved in chromatin remodeling and transcriptional regulation and play vital roles in acetylation-mediated protein-protein interactions in cells, emerging as promising new targets in epigenetic medicine for diverse human diseases, including cancers, inflammations and autoimmune disorders. In this article, the biological function, structure and classification of BRDs were introduced, and especially the research progress on inhibitors of BRDs was reviewed with focus on BET bromodomain inhibitors and non-BET bromodomain inhibitors, so as to provide some references for the development of highly active and selective inhibitors of BRDs. [Key words] bromodomain; acetylation; lysine residue; chromatin; transcriptional r