The Added Value of Assessing Ligand-Receptor Binding Kinetics in Drug Discovery

Abstract

he Added Value of Assessing Ligand–Receptor Binding Kinetics in Drug DiscoveryDong Guo†, Laura H. Heitman†, and Adriaan P. IJzerman*†† Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China† Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300 RA Leiden, The NetherlandsACS Med. Chem. Lett., 2016, 7 (9), pp 819–821DOI: 10.1021/acsmedchemlett.6b00273Publication Date (Web): August 19, 2016Copyright © 2016 American Chemical Society*E-mail: ijzerman@lacdr.leidenuniv.nl.

Abstract

In the past decade drug research community has started to appreciate the indispensable role of ligand–receptor binding kinetics (BK) in drug discovery. Next to the classical equilibrium-based drug evaluation process with affinity and potency values as outcomes, kinetic investigation of the ligand–receptor interaction can aid compound triage in the hit-to-lead campaign and provide additional information to understand the molecular mechanism of drug action. Translational models incorporating BK are emerging as well, which represent powerful tools for the prediction of in vivo effects. In this viewpoint we will summarize some recent findings and discuss and emphasize the added value of ligand–receptor binding kinetics in drug research.