共价抑制剂的研究进展  

Research Progress of Covalent Inhibitors

作　　者：董浩然 苏比丁.塔依尔 王鑫 雷晓光[1,2] Dong Haoran1,Subiding Tayier1,Wang Xin1,Lei Xiaoguang1,2(aDepartment of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871;b Peking- Tsinghua Center for Life Sciences, Beijing 10087)

机构地区：[1]北京大学化学与分子工程学院化学生物学系,北京100871 [2]北大-清华生命科学研究中心,北京100871

出　　处：《有机化学》2018年第9期2296-2306,共11页Chinese Journal of Organic Chemistry

基　　金：国家重点研发计划(No.2017YFA0505200);国家重点基础研究发展(973计划;No.2015CB856200);国家自然科学基金(Nos.21472010;21521003;21561142002;21625201)资助项目~~

摘　　要：共价抑制剂因其具有的优异的药代动力学特征,在近期的药物研发领域中起到了关键作用.共价抑制剂是一类有机小分子,能与特定的靶蛋白相互作用并形成共价键,导致蛋白质构象的改变,从而抑制蛋白质的活性.除了部分例外,通过共价抑制剂进行的蛋白质修饰通常是不可逆的.重点讨论通过迈克尔加成、亲核取代以及二硫键与蛋白质相互作用的商业共价抑制剂.有关于共价抑制剂中各种类型弹头的讨论,可以激发未来合理药物设计的灵感.The development of covalent inhibitors plays a major role in recent drug discovery due to their potential excellent pharmacokinetics. Covalent inhibitors are small organic molecules which interact with specific target proteins and form a covalent bond, resulting an alteration of the protein conformation and subsequently inhibit the protein activity. The modifications of proteins by covalent inhibitors are generally irreversible with some exceptions. In this review, the commercial covalent inhibitors that interact with proteins via Michael additions, nucleophilic substitution, or disulfide linkage are reviewed. The discussion on various types of warheads in covalent inhibitors could inspire future rational drug design.

关 键 词：共价抑制剂 弹头 药物设计 

分 类 号：R97[医药卫生—药品]