Lysine-Targeting Covalent Inhibitors.
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Date
2017-11-27Author
Pettinger, J
Jones, K
Cheeseman, MD
Type
Journal Article
Metadata
Show full item recordAbstract
Targeted covalent inhibitors have gained widespread attention in drug discovery as a validated method to circumvent acquired resistance in oncology. This strategy exploits small-molecule/protein crystal structures to design tightly binding ligands with appropriately positioned electrophilic warheads. Whilst most focus has been on targeting binding-site cysteine residues, targeting nucleophilic lysine residues can also represent a viable approach to irreversible inhibition. However, owing to the basicity of the ϵ-amino group in lysine, this strategy generates a number of specific challenges. Herein, we review the key principles for inhibitor design, give historical examples, and present recent developments that demonstrate the potential of lysine targeting for future drug discovery.
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Research team
Medicinal Chemistry 3
Language
eng
Date accepted
2017-08-29
License start date
2017-11
Citation
Angewandte Chemie (International ed. in English), 2017, 56 (48), pp. 15200 - 15209
Publisher
WILEY-V C H VERLAG GMBH