Inhibitor Design & Analysis

This lecture provides an overview of inhibitor design and analysis, focusing on evaluating next-generation covalent drugs. Topics include fundamental modes of drug action, residue-specific target engagement, and the importance of targeting cysteine residues. The lecture discusses the distinction between reversible and irreversible binders, the reactivity of nucleophilic amino acids, and the various faces of protein cysteines. It also delves into the kinetic reactivity and binding affinity of covalent inhibitors, emphasizing the correlation with cellular potency. The lecture concludes with a discussion on segregating kinetic reactivity and binding affinity in drug development.