Covalent Inhibitors

In the past decade, covalent small molecules have seen a surge, both in clinical drugs as well as in research tools to study protein functions. However, similar to reversible small-molecule probes, the quality of covalent molecular probes is crucial for their value in cell biology studies. Rigorous evaluation of covalent molecules is necessary to state with confidence that they are specific modulators of a protein target. In particular, the time-dependency of covalent inhibitors needs to be taken into consideration. Based on the publication by Hartung et al, the Chemical Probes Team proposes the following criteria for covalent chemical probes.

Hartung I.V. et al (2023) J Med Chem (DOI: 10.1021/acs.jmedchem.3c00550))