title: Kinetic Profile of Neuropeptide-Receptor Interactions.
abstract: Currently, drug discovery focusses only on quantifying pharmacological parameters, sometimes including binding kinetics, of drug candidates. For a complete understanding of a drug's desired binding kinetics, the kinetics of both the target and its endogenous ligands should be considered. This is because the release and binding kinetics of endogenous ligands in addition to receptor internalization rates are significant contributors to drug-target interactions. Here, we discuss the kinetic profile of three neuropeptides and their receptors; gonadotropin-releasing hormone receptor (GnRHR), neuropeptide Y receptors, and corticotropin-releasing factor receptor 1 (CRF1R). These three examples provide new insights into the importance of kinetic profiles which could improve the understanding of desired drug-target binding kinetics and advance drug discovery for various neurological and psychiatric illnesses.
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors: Indira
authors: I
authors: Nederpelt
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors: Julia
authors: J
authors: Bunnik
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors: Adriaan P
authors: AP
authors: IJzerman
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. Electronic address: l.h.heitman@lacdr.leidenuniv.nl.
authors: Laura H
authors: LH
authors: Heitman
mesh_terms: D000818:Animals; D055808:Drug Discovery; D006801:Humans; D007700:Kinetics; D009479:Neuropeptides / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D018013:Receptors, Neuropeptide
keywords: G-protein-coupled receptor; binding kinetics; endogenous ligand; internalization kinetics; neuropeptide; peptide release