Advances in covalent drug discovery.

ABSTRACT: Covalent drugs have been used to treat diseases for more than a century, but tools that facilitate the rational design of covalent drugs have emerged more recently. The purposeful addition of reactive functional groups to existing ligands can enable potent and selective inhibition of target proteins, as demonstrated by the covalent epidermal growth factor receptor (EGFR) and Bruton's tyrosine kinase (BTK) inhibitors used to treat various cancers. Moreover, the identification of covalent ligands through 'electrophile-first' approaches has also led to the discovery of covalent drugs, such as covalent inhibitors for KRAS(G12C) and SARS-CoV-2 main protease. In particular, the discovery of KRAS(G12C) inhibitors validates the use of covalent screening technologies, which have become more powerfu

SUBMITTER: Boike L 

PROVIDER: S-EPMC9403961 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature