Covalent fragment technologies for therapeutic target discovery and validation

Advances in genomic analyses enable the identification of proteins that are associated with disease. In order to validate these targets for prioritisation in drug discovery programmes, tool molecules are required to demonstrate that a ligand can have a disease-modifying effect. Currently, as tools are reported for only a fraction of the proteome, platforms for expedient ligand discovery are essential to leverage insights from genomic analyses. The use of electrophilic fragment libraries has emerged within chemical biology as a powerful approach for the identification of fragment–protein interactions, particularly in a cellular context.