Drug-Target Association Kinetics in Drug Discovery

The important role of ligand-receptor binding kinetics in drug design and discovery is increasingly recognized by the drug research community. Over the past decade, accumulating evidence has shown that optimizing the ligand's dissociation rate constant can lead to desirable duration of in vivo target occupancy and, hence, improved pharmacodynamic properties. However, the association rate constant as a pharmacological principle remains less investigated, whereas it can play an equally important role in the selection of drug candidates. This review provides a compilation and discussion of otherwise scarce and dispersed information on this topic, bringing to light the importance of drug-target association in kinetics-directed drug design and discovery.