组蛋白去乙酰化酶6及其选择性抑制剂的研究进展  

Progress in the Research of Histone Deacetylase 6 and Its Selective Inhibitors

作　　者：刘婷[1] 亓云鹏[1] 宋云龙[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《药学进展》2016年第11期848-857,共10页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金(No.81172928)

摘　　要：组蛋白去乙酰化酶6(HDAC6)是组蛋白去乙酰化酶(HDACs)Ⅱb家族中的一员,主要催化α-微管蛋白、热休克蛋白Hsp90、皮质肌动蛋白及过氧化物还原酶等的去乙酰化。HDAC6与肿瘤、神经退行性疾病、炎症、自身免疫应答、细菌感染及心脏病等诸多疾病的病理生理进程密切相关,是一个极具应用前景的药物靶标。选择性HDAC6抑制剂是目前该领域的研究热点,有望克服广谱HDAC抑制剂存在的选择性差、副作用大等缺点。综述HDAC6的结构、生化功能、与疾病的关系及其选择性抑制剂的研究进展,为开发新型选择性HDAC6抑制剂提供参考。Histone deacetylase 6（HDAC6）, a member of Ⅱb histone deacetylases（HDACs） family, mainly catalyzes the deacetylation of α-tubulin, heat shock protein 90（Hsp90）, cortactin and peroxiredoxin. It is implicated in the pathogenesis and progression of tumors, neurodegenerative diseases, inflammation, autoimmune responses, bacterial infections, cardiac diseases, etc. Therefore, HDAC6 is a promising target with multiple potential applications. Selective HDAC6 inhibitors are hot spot in this field of research, and are expected to overcome the defects of broad-spectrum histone deacetylase inhibitors（HDACi） such as poor selectivity and severe side effects. The structure and biochemical function of HDAC6, its involvement in diseases as well as advances in the research of selective inhibitors were reviewed herein, so as to provide references for the development of novel selective HDAC6 inhibitors.

关 键 词：组蛋白去乙酰化酶6 选择性抑制剂 构效关系 

分 类 号：R979.1[医药卫生—药品]