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

Sara Núñez, Jennifer Venhorst, Chris G. Kruse
2012 Drug Discovery Today  
The utilization of the kinetic and thermodynamic signatures of preclinical leads is proving pivotal in their triage and rational optimization towards clinical candidates with maximal in vivo efficacy devoid of adverse events. 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
more » ... uccessful 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.
doi:10.1016/j.drudis.2011.06.013 pmid:21777691 fatcat:paqphwwlu5frxpgbalze2nqvdq