Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (9): 2296-2306.DOI: 10.6023/cjoc201804018 Previous Articles     Next Articles

Special Issue: 合成科学

Reviews

共价抑制剂的研究进展

董浩然a, 苏比丁·塔依尔a, 王鑫a, 雷晓光a,b   

  1. a 北京大学化学与分子工程学院化学生物学系 北京 100871;
    b 北大-清华生命科学研究中心 北京 100871
  • 收稿日期:2018-04-10 修回日期:2018-06-19 出版日期:2018-09-25 发布日期:2018-07-24
  • 通讯作者: 雷晓光 E-mail:xglei@pku.edu.cn
  • 基金资助:

    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.

Research Progress of Covalent Inhibitors

Dong Haorana, Subiding Tayiera, Wang Xina, Lei Xiaoguanga,b   

  1. a Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871;
    b Peking-Tsinghua Center for Life Sciences, Beijing 100871
  • Received:2018-04-10 Revised:2018-06-19 Online:2018-09-25 Published:2018-07-24
  • Contact: 10.6023/cjoc201804018 E-mail:xglei@pku.edu.cn
  • Supported by:

    Project supported by the National Key Research and Development Program of China (No. 2017YFA0505200), the National Key Fundamental Research and Development of China (973 Program, No. 2015CB856200), the National Natural Science Foundation of China (Nos. 21472010, 21521003, 21561142002, 21625201).

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.

Key words: covalent inhibitors, warheads, drug design