title: Impact, determination and prediction of drug-receptor residence times for GPCRs.
abstract: The residence time of a ligand on a GPCR of interest has become an optimization parameter in many examples in drug design. Long residence times can counterbalance unfavorable pharmacokinetic parameters, contributing to compound safety, and short residence times can be a tool to avoid target related side effects. Unlike the prediction and interpretation of the structure-activity relationship (SAR) of a ligand class on a receptor, the understanding and prediction of the structure-kinetics relationship (SKR) is much more demanding. Experimental and computational approaches are described, which serve to either rationalize SKR or to predict the kinetic parameters such as on-rates and off-rates.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Lead Identification and Optimization Support, Birkendorfer Str. 65, D-88397 Biberach a.d. Riss, Germany. Electronic address: christofer.tautermann@boehringer-ingelheim.com.
authors.forename: Christofer S
authors.initials: CS
authors.lastname: Tautermann
mesh_terms: D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D007700:Kinetics; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D043562:Receptors, G-Protein-Coupled