title: The drug-target residence time model: a 10-year retrospective.
abstract: The drug-target residence time model was first introduced in 2006 and has been broadly adopted across the chemical biology, biotechnology and pharmaceutical communities. While traditional in vitro methods view drug-target interactions exclusively in terms of equilibrium affinity, the residence time model takes into account the conformational dynamics of target macromolecules that affect drug binding and dissociation. The key tenet of this model is that the lifetime (or residence time) of the binary drug-target complex, and not the binding affinity per se, dictates much of the in vivo pharmacological activity. Here, this model is revisited and key applications of it over the past 10 years are highlighted.
authors.affiliation: Epizyme Inc., 400 Technology Square, Cambridge, Massachusetts 02139, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Copeland
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D046911:Macromolecular Substances