Citation: Dong Haoran, Subiding Tayier, Wang Xin, Lei Xiaoguang. Research Progress of Covalent Inhibitors[J]. Chinese Journal of Organic Chemistry, ;2018, 38(9): 2296-2306. doi: 10.6023/cjoc201804018 shu

Research Progress of Covalent Inhibitors

a.
Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871
b.
Peking-Tsinghua Center for Life Sciences, Beijing 100871

Corresponding author: Lei Xiaoguang, xglei@pku.edu.cn
Received Date: 10 April 2018
Revised Date: 19 June 2018
Available Online: 24 September 2018
Fund Project: the National Key Fundamental Research and Development of China (973 Program) 2015CB856200the National Key Research and Development Program of China 2017YFA0505200the National Natural Science Foundation of China 21625201the National Natural Science Foundation of China 21521003Project 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 National Natural Science Foundation of China 21472010the National Natural Science Foundation of China 21561142002

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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.
- covalent inhibitors,
- warheads,
- drug design
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