基于蛋白质组学的组蛋白表观遗传酶抑制剂研究进展  

Advances in histone epigenetic enzyme inhibitors based on proteomics

作　　者：刘权 王璐璐 徐骏宇 谭敏佳 LIU Quan;WANG Lu-lu;XU Jun-yu;TAN Min-jia(State Key Laboratory of New Drug Research,Shanghai Institute of Materia Medica,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;School of Pharmacy,Nanjing University ofChinese Medicine,Nanjing 210023,China)

机构地区：[1]中国科学院上海药物研究所,新药研究国家重点实验室,上海201203 [2]中国科学院大学,北京100049 [3]南京中医药大学药学院,江苏南京210023

出　　处：《药学学报》2023年第9期2541-2550,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(22225702)。

摘　　要：组蛋白作为真核生物体细胞染色质上核小体的重要组成部分,其上发生的如乙酰化和甲基化等能够调控表观遗传的翻译后修饰,在肿瘤疾病发生、发展的过程中发挥了重要的作用。与此同时,靶向干预甲基转移酶和去乙酰化酶的药物开发,为肿瘤疾病提供了新的治疗策略。基于生物质谱技术的蛋白质组学,可解析疾病进展过程中药物作用下组蛋白修饰的全景变化,进而为揭示药物作用及其耐药机制,研究新型药物联用策略提供重要支持。本文重点介绍了包括甲基转移酶抑制剂和去乙酰化酶抑制剂在内的多种组蛋白修饰酶抑制剂的蛋白质组学研究进展和现状,有助于了解蛋白质组学在组蛋白表观遗传酶抑制剂方面的最新研究,为蛋白质组学在更多表观遗传酶及其特异性抑制剂的研究中提供新线索。As an important component of nucleosomes on the chromatin of eukaryotic cells,histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation.In addition,development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment.Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression,which in turn provides important support for revealing drug action mechanism,drug resistance mechanism,and investigating novel drug combination strategies.This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors,including methyltransferase inhibitors and histone deacetylase inhibitors,which will help to understand the current and further utilization of proteomics in studying histone modifications.

关 键 词：蛋白质组学 组蛋白修饰 组蛋白甲基转移酶 组蛋白去乙酰化酶 表观遗传抑制剂 

分 类 号：R966[医药卫生—药理学]