The impact of binding thermodynamics on medicinal chemistry optimizations

Abstract

Ligand binding thermodynamics has been attracted considerable interest in the past decade owing to the recognized relation between binding thermodynamic profile and the physicochemical and druglike properties of compounds. In this review, the relation between optimization strategies and ligand properties is presented based on the structural and thermodynamic analysis of ligand-protein complex formation. The control of the binding thermodynamic profile is beneficial for the balanced affinity and physicochemical properties of drug candidates, and early phase optimization gives more opportunity to this control.