Work

Covalent drug discovery: Progress against key targets, emerging strategies and lessons learnt

Year: 2026

Type: article

Abstract: Covalent drug discovery is currently experiencing a boom in industrial and academic interest. To date, at least 75 covalent drugs have received regulatory approval, targeting both traditional target classes and more challenging proteins for which other approaches failed. In many cases, unique aspects of covalent targeting are essential for the efficacy of the drug molecule. Famous successes include the discovery of therapies targeting KRAS G12C , EGFR L858R, T790M and BTK, whilst molecules targeting KRAS G12D , WRN helicase and p53 Y220C have recently been disclosed and will represent significant achievements if they receive regulatory approval. Increased interest in the field has catalysed innovation and advanced theoretical understanding of the distinct considerations resulting from the covalent interaction. Here, we review progress against key covalent drug targets, emphasising notable molecules which exemplify the advantages of a covalent approach.

Source: British Journal of Pharmacology

DOI: 10.1111/bph.70344

Authors: Charles P. Brown, Alan Armstrong, David J. Mann

Institution: Imperial College London

Language: English

Topic: Protein Degradation and Inhibitors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,780