The resurgence of covalent drugs

Nat Rev Drug Discov. 2011 Apr;10(4):307-17. doi: 10.1038/nrd3410.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems*
  • Drug Design*
  • Drug Discovery / methods
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*
  • Structure-Activity Relationship


  • Pharmaceutical Preparations