Quon, T., Lin, L.-C., Ganguly, A., Tobin, A. B. and Milligan, G. (2020) Therapeutic opportunities and challenges in targeting the orphan G protein-coupled receptor GPR35. ACS Pharmacology and Translational Science, 3(5), pp. 801-812. (doi: 10.1021/acsptsci.0c00079) (PMID:33073184)
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Abstract
GPR35 is a class A, rhodopsin-like G protein-coupled receptor (GPCR) first identified more than 20 years ago. In the intervening period identification of strong expression in the lower intestine and colon, as well as in a variety of immune cells including monocytes and a variety of dendritic cells, and in dorsal root ganglia, has suggested potential therapeutic opportunities in targeting this receptor in a range of conditions. GPR35 is, however, unusual in a variety of ways that challenge routes to translation. These include that although a substantial range and diversity of endogenous ligands have been suggested as agonist partners for this receptor it officially remains defined as an ‘orphan’ GPCR; that humans express two distinct protein isoform sequences whilst rodents express only a single form, and that the pharmacology of the human and rodent orthologues of GPR35 is very distinct, with variation between rat and mouse GPR35 as marked as between either of these species and the human forms. 2 Herein we provide perspectives on each of the topics above as well as suggesting ways to overcome the challenges currently hindering potential translation. These include better understanding of the extent and molecular basis for species selective GPR35 pharmacology and the production of novel mouse models in which both ‘on-target’ and ‘off-target’ effects of presumptive GPR35 ligands can be better defined as well as clear understanding in human of isoform expression profile and its significance at both tissue and individual cell level.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Quon, Dr Tezz and Ganguly, Amlan and Milligan, Professor Graeme and Tobin, Andrew and Lin, Dr Li-Chiung |
| Authors: | Quon, T., Lin, L.-C., Ganguly, A., Tobin, A. B., and Milligan, G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | ACS Pharmacology and Translational Science |
| Publisher: | American Chemical Society |
| ISSN: | 2575-9108 |
| ISSN (Online): | 2575-9108 |
| Published Online: | 29 July 2020 |
| Copyright Holders: | Copyright © 2020 American Chemical Society |
| First Published: | First published in ACS Pharmacology and Translational Science 3(5):801-812 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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