Therapeutic implications of target residence time

While potency of drugs has been considered the main criterion defining therapeutic utility in vivo, target residence time (RT, the time the ligand associates with the target in vivo) is also important, and studies have shown that in some cases, it is more important than potency. New data in this area have contributed toward the substantive detection and manipulation of RT for therapeutic increased value on the following two fronts: (1) new and better techniques to assess ligand-target kinetics and (2) new appreciation of ligand types (i.e. allosteric modulators) and mechanisms of ligand binding including the temporal implications of binding to cryptic pockets on GPCRs. These data will be discussed.