组蛋白去乙酰化酶8选择性抑制剂的研究进展

组蛋白去乙酰化酶8(HDAC8)属于Ⅰ类锌离子依赖性的组蛋白去乙酰化酶，与人类病理生理学密切相关。HDAC8参与体内多种关键信号通路，是多种疾病的治疗靶点。随着对HDAC8晶体结构研究的不断深入，多种结构类型的HDAC8抑制剂被报道，主要分为苯基氧肟酸类、吲哚类、邻芳基N-羟基肉桂酰胺类和氮杂环丁酮类等。寻找比泛HDAC抑制剂不良反应小的高效选择性HDAC8抑制剂是目前研究的热点。本文综述了HDAC8的结构、功能及选择性抑制剂的研究进展。

Advances in histone deacetylase 8 selective inhibitors

Histone deacetylase 8(HDAC8)is a zinc-dependent class I histone deacetylase, closely related to human pathophysiology. HDAC8 involves in various critical signaling networks and is implicated as a therapeutic target in various diseases, including cancer, X-linked intellectual disability and parasitic infections. More and more selective HDAC8 inhibitors have been developed based on deepening study of its well-characterized crystal structure. They are mainly divided into several categories such as phenyl hydroxamic acids, indoles, ortho-aryl-N-hydroxycinnamides, azetidinones etc. . Current challenges remain in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors. Herein, we reviewed the progress in the study of structure and functions of HDAC8 as well as the development of selective HDAC8 inhibitors.