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Lookup NU author(s): Dr Suzannah HarnorORCiD,
Dr Celine CanoORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Royal Society of Chemistry, 2022.
For re-use rights please refer to the publisher's terms and conditions.
© 2022 RSC. In recent years, the development of targeted covalent inhibitors has gained popularity around the world. Specific groups (electrophilic warheads) form irreversible bonds with the side chain of nucleophilic amino acid residues, thus changing the function of biological targets such as proteins. Since the first targeted covalent inhibitor was disclosed in the 1990s, great efforts have been made to develop covalent ligands from known reversible leads or drugs by addition of tolerated electrophilic warheads. However, high reactivity and “off-target” toxicity remain challenging issues. This review covers the concept of targeted covalent inhibition to diseases, discusses traditional and interdisciplinary strategies of cysteine-focused covalent drug discovery, and exhibits newly disclosed electrophilic warheads majorly targeting the cysteine residue. Successful applications to address the challenges of designing effective covalent drugs are also introduced.
Author(s): Gai C, Harnor SJ, Zhang S, Cano C, Zhuang C, Zhao Q
Publication type: Article
Publication status: Published
Journal: RSC Medicinal Chemistry
Print publication date: 01/12/2022
Online publication date: 11/10/2022
Acceptance date: 20/09/2022
Date deposited: 12/12/2022
ISSN (electronic): 2632-8682
Publisher: Royal Society of Chemistry
ePrints DOI: 10.57711/s4jc-b767
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