组蛋白去甲基化酶5的结构、功能及其抑制剂研究进展  

Progress of Research on the Structures,Functions of Histone Demethylase 5 and Related Inhibitors

作　　者：唐凯[1] 左佳辉 余斌[1] 刘宏民[1] TANG Kai;ZUO Jiahui;YU Bin;LIU Hongmin(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学药学院,河南郑州450001

出　　处：《药学进展》2020年第9期644-655,共12页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金项目(No.81703326,No.81973177)。

摘　　要：组蛋白去甲基化酶5(KDM5)属于JMJD(jumonji domain containing)蛋白家族,KDM5包含JmjC、PHD、ARID等特征结构域,能够特异性去除组蛋白3第4位赖氨酸(H3K4)上甲基化修饰,被认为是潜在的抗肿瘤药物作用靶标。目前已有较多的KDM5抑制剂被报道,其中多个小分子抑制剂如CPI-455、EPT103182等已经进入临床前研究阶段。通过对KDM5的结构、生物学功能及代表性抑制剂展开综述,为新型KDM5抑制剂的结构设计以及优化提供参考。Lysine-specific demethylases 5(KDM5)belong to the JMJD protein family and consist of JmjC,PHD,ARID and other characteristic domains.KDM5 can specifically remove the methyl groups of histone H3 lysine 4(H3K4),and thus have been considered as potential therapeutic targets.To date,there have been reports of a large number of KDM5 inhibitors,some of which such as CPI-455 and EPT103182 have advanced into preclinical studies.In this review,we mainly focus on the recent progress on the protein structures and biological functions of KDM5 and their representative inhibitors,aiming to provide guidance for the structural design and optimization of novel KDM5 inhibitors.

关 键 词：表观调控 组蛋白去甲基化酶5 小分子抑制剂 肿瘤治疗 

分 类 号：R914[医药卫生—药物化学]