药学学报, 2017, 52(7): 1102-1109
引用本文:
杨波, 陈彦清, 张良明, 杨胜勇, 李琳丽. 组蛋白赖氨酸去甲基化酶抑制剂研究进展[J]. 药学学报, 2017, 52(7): 1102-1109.
YANG Bo, CHEN Yan-qing, ZHANG Liang-ming, YANG Sheng-yong, LI Lin-li. Research progress in histone lysine demethylases inhibitors[J]. Acta Pharmaceutica Sinica, 2017, 52(7): 1102-1109.

组蛋白赖氨酸去甲基化酶抑制剂研究进展
杨波1,2, 陈彦清1, 张良明1, 杨胜勇2, 李琳丽2
1. 攀枝花市中心医院, 四川 攀枝花 617067;
2. 四川大学华西医学中心, 四川 成都 610041
摘要:
组蛋白赖氨酸的甲基化在表观遗传调控中起着关键作用。组蛋白赖氨酸甲基化主要发生在H3的K4、K9、K27、K36、K79和H4的K20上,不同位点的甲基化修饰将导致转录激活或沉默。组蛋白赖氨酸甲基转移酶(HKMTs)和组蛋白赖氨酸去甲基化酶(HKDMs)共同调控着组蛋白赖氨酸的甲基化修饰状态。据报道,HKDMs的错误调控与多种肿瘤的发生和耐药有关,受到了更多的关注。因此,HKDMs抑制剂的研究开发意义重大,既可作为小分子探针研究其生物学功能,也有望开发为新型抗肿瘤药物。本文将对HKDMs抑制剂及其在疾病治疗方面的潜力进行综述。
关键词:    表观遗传      组蛋白赖氨酸去甲基化酶      抑制剂      癌症治疗     
Research progress in histone lysine demethylases inhibitors
YANG Bo1,2, CHEN Yan-qing1, ZHANG Liang-ming1, YANG Sheng-yong2, LI Lin-li2
1. Panzhihua Central Hospital, Panzihua 617067, China;
2. West China Center of Medical Sciences, Sichuan University, Chengdu 610041, China
Abstract:
The methylation of histone lysine plays a pivotal role in epigenetic regulation of gene expression. Histone lysine methylation modifications have 5 sites within histone H3(K4, K9, K27, K36, K79)and 1 site within histone H4(K20). Methylation at various sites has been shown to lead to transcriptional activation or silencing. Histone lysine methyltransferases(HKMTs)and histone lysine demethylases(HKDMs)collectively regulate the methylation modification state of histone lysine. It was reported that the mis-regulation of HKDMs is associated with the occurring and resistance of numerous malignant tumors, so more and more attention are received to HKDMs. Therefore, it is great significant in the study and development of HKDMs inhibitors. The inhibitors could be served not only as a tool in the investigation of the biological function, but also could be used as novel anti-cancer agents in the anticancer therapy. In this review, we provide a short summary of the HKDMs inhibitors recently reported and their potential in the treatment of diseases.
Key words:    epigenetics    histone lysine demethylases    inhibitor    anticancer therapy   
收稿日期: 2017-01-04
DOI: 10.16438/j.0513-4870.2017-0012
基金项目: 国家自然科学基金资助项目(81473140)
通讯作者: 杨波,Tel/Fax:86-812-2238461,E-mail:964883171@qq.com
Email: 964883171@qq.com
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