At DDS we have provided support to several teams with covalent binders in their pipeline.
An increase in covalent binder drug candidates has been observed in the drug discovery arena in recent years, and we wanted to share a PK/PD paper that may be valuable for clients exploring this space: A Perspective on the Kinetics of Covalent and Irreversible Inhibition by John M. Strelow.
Rather than focusing only on endpoint potency metrics like IC₅₀, the paper highlights the importance of kinetic parameters such as kinact/KI for understanding efficiency of inactivation, coupled with unbound plasma concentration/time profile to translate to in vivo performance. It’s a practical read for anyone interested in developing or evaluating covalent compounds.