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); Sadiq, S Kashif (Heidelberg Institute for Theoretical Studies); 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); Georgi, Victoria (Bayer AG); 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); de Lange, Elizabeth Cunera Maria (Leiden University); IJzerman, Adriaan P. (Leiden University); Müller-Fahrnow, Anke (Bayer AG); Ecker, Gerhard F

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.

Date of publication:6.2017
Journal title:Drug Discovery Today
Peer reviewed:true
Digital Object Identifier (DOI):
Bibliographical note:Copyright © 2017. Published by Elsevier Ltd.
Publication Type:Article