Target-drug interactions: first principles and their application to drug discovery

Abstract

In this review, we begin by introducing the basic principles of kinetics and thermodynamics of target-drug binding within the context of drug discovery. In addition, we present a meta-analysis of the recent literature describing the kinetic and thermodynamic resolution of successful clinical candidates with diverse mechanisms of action. We finish by discussing the best practices in the triage and chemical optimization towards clinical candidates with maximal in vivo efficacy devoid of adverse events.