组蛋白甲基转移酶G9a抑制剂的研究进展  

Research Progress in Inhibitors of Histone Methyltransferase G9a

作　　者：王楚慧 赵铜鑫 陈维琳[1] 湛云鹏 张涵煦 尤启冬[1,2] 郭小可[1,2] WANG Chuhui;ZHAO Tongxin;CHEN Weilin;ZHAN Yunpeng;ZHANG Hanxu;YOU Qidong;GUO Xiaoke(Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China)

机构地区：[1]中国药科大学江苏省药物分子设计与成药性优化重点实验室,江苏南京210009 [2]中国药科大学药物化学教研室,江苏南京210009

出　　处：《药学进展》2018年第4期284-293,共10页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金青年基金(No.81502915);国家级大学生创新创业训练计划项目(No.G15052);中国药科大学药学基地科研训练及科研能力提高项目(No.J1310032)

摘　　要：组蛋白甲基转移酶G9a可以催化组蛋白H3K9发生单甲基化、二甲基化及缓慢的三甲基化,也可以特异性地催化一些非组蛋白如p53的甲基化。G9a参与体内许多生物学过程,并与人类的各种疾病特别是肿瘤的发生和发展密切相关,被认为是一个具有广阔前景的肿瘤治疗新靶标。因此,G9a抑制剂的开发受到广泛关注。综述近10年报道的G9a小分子抑制剂的研究进展,以期为现有抑制剂的临床进展和新型抑制剂的开发提供参考。Histone methyltransferase G9a is responsible for catalyzing the mono-, di-and slowly trimethylation of histone H3 lysine 9（H3K9）. It can also specifically methylate lysine 373 in tumor suppressor p53. G9a plays crucial roles in diverse biological processes and various human diseases especially in the pathogenesis and progress of cancer. It is considered as a promising novel antineoplastic target. Hence, the development of its inhibitors has received increased attention. The research advances in different classes of small molecular inhibitors of G9a reported over the past decade were reviewed, so as to provide reference for the clinical development of small molecular inhibitors and the discovery of novel inhibitors.

关 键 词：G9a 抗肿瘤 小分子抑制剂 甲基转移酶 

分 类 号：R914.4[医药卫生—药物化学] R979.1[医药卫生—药学]