Employing novel animal models in the design of clinically efficacious GPCR ligands

Bradley, S. J. , Riaz, S. A. and Tobin, A. (2014) Employing novel animal models in the design of clinically efficacious GPCR ligands. Current Opinion in Cell Biology, 27, pp. 117-125. (doi: 10.1016/j.ceb.2013.12.002) (PMID:24680437) (PMCID:PMC3989050)

Abstract

The headline success of targeting GPCRs in human diseases has masked the fact that many GPCR drug discovery programmes fail. This is despite a substantial increase in our understanding of GPCR pharmacology that has provided an array of ligands that target both orthosteric and allosteric sites as well as ligands that show stimulus bias. From this plethora of pharmacological possibilities, can we design ligand properties that would deliver maximal clinical efficacy with lowest toxicity? This may be achieved through animal models that both validate a particular GPCR as a target as well as revealing the signalling mechanisms that underlie receptor-mediated physiological and clinical responses. In this article, we examine recent novel transgenic models being employed to address this issue.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tobin, Andrew and Bradley, Dr Sophie
• Authors: Bradley, S. J., Riaz, S. A., and Tobin, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Research Group: Cell Biology
• Journal Name: Current Opinion in Cell Biology
• Publisher: Elsevier
• ISSN: 0955-0674
• ISSN (Online): 1879-0410
• Copyright Holders: Copyright © 2013 The Authors
• First Published: First published in Current Opinion in Cell Biology 27:117-125
• Publisher Policy: Reproduced under a Creative Commons License