Covalent hits and where to find them

Abstract

Covalent hits for drug discovery campaigns are neither fantastic beasts nor mythical creatures, they can be routinely identified through electrophile-first screening campaigns using a suite of different techniques. These include biophysical and biochemical methods, cellular approaches, and DNA-encoded libraries. Employing best practice, however, is critical to success. The purpose of this review is to look at state of the art covalent hit identification, how to identify hits from a covalent library and how to select compounds for medicinal chemistry programmes.

Keywords: Covalent; DEL; Hit identification; Irreversible; Mass spectrometry; Screening.