Drug development of covalent inhibitors

Covalent inhibitors are a unique class of small molecule drugs that form covalent bonds with their intended protein target. Due to this unique inhibition pathway, traditional measures of inhibition potency are insufficient to characterize and optimize their discovery and development. High inhibitory efficiency, extended pharmacological effects, and the potential to overcome resistance mechanisms are hallmarks of drugs that are covalent inhibitors. While theoretical concerns of potential off-target or immunological effects persist, covalent inhibitors continue to demonstrate reasonable safety profiles in the clinical situation and have enabled targeting of proteins that were once considered undruggable.