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Updated: Jun 3, 2026

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
Published on: February 28, 2025
The resurgence of covalent drugs
Juswinder Singh1, Russell C Petter, Thomas A Baillie
1Avila Therapeutics, 100 Beaver Street, Waltham, Massachusetts 02453, USA. jsingh@avilatx.com
Abstract:
Covalent drugs have proved to be successful therapies for various indications, but largely owing to safety concerns, they are rarely considered when initiating a target-directed drug discovery project. There is a need to reassess this important class of drugs, and to reconcile the discordance between the historic success of covalent drugs and the reluctance of most drug discovery teams to include them in their armamentarium. This review surveys the prevalence and pharmacological advantages of covalent drugs, discusses how potential risks and challenges may be addressed through innovative design, and presents the broad opportunities provided by targeted covalent inhibitors.
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