Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84

Marsango, S., Barki, N., Jenkins, L. , Tobin, A. B. and Milligan, G. (2022) Therapeutic validation of an orphan G protein-coupled receptor: the case of GPR84. British Journal of Pharmacology, 179(14), pp. 3529-3541. (doi: 10.1111/bph.15248) (PMID:32869860) (PMCID:PMC9361006)

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Despite the importance of members of the G protein‐coupled receptor (GPCR) superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. In certain cases even the endogenous ligand(s) that activates them remains undefined or uncertain. Such GPCRs are designated as orphan receptors and although this is frequently also associated with a limited pharmacological palette of selective ligands, this does not mean that there is a lack of interest in better understanding and assessing specific orphan GPCRs as novel therapeutic opportunities. GPR84 is an example. Expression of GPR84 is strongly upregulated in immune cells in a range of pro‐inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Jenkins, Mrs Laura and Milligan, Professor Graeme and Tobin, Andrew and Barki, Ms Natasja and Marsango, Dr Sara
Authors: Marsango, S., Barki, N., Jenkins, L., Tobin, A. B., and Milligan, G.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:British Journal of Pharmacology
ISSN (Online):1476-5381
Published Online:01 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in British Journal of Pharmacology 179(14): 3529-3541
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305987IPA Responsive Mode BBSRC Resubmission GPR84Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/T000562/1Institute of Molecular, Cell & Systems Biology