Kinetics for Drug Discovery

Subtitle:an industry-driven effort to target drug residence time
Authors/others:Schuetz, Doris A; de Witte, Wilhelmus Egbertus Arnout (Leiden University); Wong, Yin Cheong (Leiden University); Knasmueller, Bernhard; Richter, Lars; Kokh, Daria B (Heidelberg Institute for Theoretical Studies HITS gGmbH); Sadiq, S Kashif (Heidelberg Institute for Theoretical Studies HITS gGmbH); Bosma, Reggie (Vrije Universiteit Amsterdam); Nederpelt, Indira (Leiden University); Heitman, Laura H (Leiden University); Segala, Elena (Heptares Therapeutics Ltd.); Amaral, Marta (Merck KGaA); Guo, Dong (Leiden University); Andres, Dorothee (Bayer AG, Drug Discovery, Pharmaceuticals, Lead Discovery Berlin, Müllerstr. 178, 13353 Berlin, Germany.); Georgi, Victoria (Bayer AG, Drug Discovery, Pharmaceuticals, Lead Discovery Berlin, Müllerstr. 178, 13353 Berlin, Germany.); Stoddart, Leigh A (University of Nottingham); Hill, Steve (University of Nottingham); Cooke, Robert M (Heptares Therapeutics Ltd.); De Graaf, Chris (Vrije Universiteit Amsterdam); Leurs, Rob (Vrije Universiteit Amsterdam); Frech, Matthias (Merck KGaA); Wade, Rebecca C (Heidelberg Institute for Theoretical Studies HITS gGmbH); de Lange, Elizabeth Cunera Maria (Leiden University); IJzerman, Adriaan P. (Leiden University); Müller-Fahrnow, Anke (Bayer AG, Drug Discovery, Pharmaceuticals, Lead Discovery Berlin, Müllerstr. 178, 13353 Berlin, Germany.); Ecker, Gerhard F
Abstract:

A considerable number of approved drugs show non-equilibrium binding characteristics, emphasizing the potential role of drug residence times for in vivo efficacy. Therefore, a detailed understanding of the kinetics of association and dissociation of a target-ligand complex might provide crucial insight into the molecular mechanism-of-action of a compound. This deeper understanding will help to improve decision making in drug discovery, thus leading to a better selection of interesting compounds to be profiled further. In this review, we highlight the contributions of the Kinetics for Drug Discovery (K4DD) Consortium, which targets major open questions related to binding kinetics in an industry-driven public-private partnership.

Language:English
Date of publication:13.4.2017
Journal title:Drug Discovery Today
Peer reviewed:true
Links:
Digital Object Identifier (DOI):http://dx.doi.org/10.1016/j.drudis.2017.02.002
Bibliographical note:Copyright © 2017. Published by Elsevier Ltd.
Publication Type:Article
State:E-pub ahead of print
Portal:https://ucris.univie.ac.at/portal/en/publications/kinetics-for-drug-discovery(2d3ed24c-4a33-4134-bd73-63896b8bbf18).html