Nature Reviews Drug Discovery 10, 307-317 (April 2011) | doi:10.1038/nrd3410

The resurgence of covalent drugs

Juswinder Singh1, Russell C. Petter1, Thomas A. Baillie2 & Adrian Whitty3  About the authors


Covalent drugs haveproved 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.

Author affiliations

  1. Avila Therapeutics, 100 Beaver Street, Waltham, Massachusetts 02453, USA.
  2. School of Pharmacy, University of Washington, Seattle, Washington 98195, USA.
  3. Department of Chemistry, Boston University, Metcalf Science Center, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.

Correspondence to: Juswinder Singh1 Email: