Complex pharmacology of free fatty acid receptors

Milligan, G. , Shimpukade, B., Ulven, T. and Hudson, B. D. (2017) Complex pharmacology of free fatty acid receptors. Chemical Reviews, 117(1), pp. 67-110. (doi: 10.1021/acs.chemrev.6b00056) (PMID:27299848)

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Abstract

G protein-coupled receptors (GPCRs) are historically the most successful family of drug targets. In recent times it has become clear that the pharmacology of these receptors is far more complex than previously imagined. Understanding of the pharmacological regulation of GPCRs now extends beyond simple competitive agonism or antagonism by ligands interacting with the orthosteric binding site of the receptor to incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, constitutive activity, and inverse agonism. Herein, we consider how evolving concepts of GPCR pharmacology have shaped understanding of the complex pharmacology of receptors that recognize and are activated by nonesterified or “free” fatty acids (FFAs). The FFA family of receptors is a recently deorphanized set of GPCRs, the members of which are now receiving substantial interest as novel targets for the treatment of metabolic and inflammatory diseases. Further understanding of the complex pharmacology of these receptors will be critical to unlocking their ultimate therapeutic potential.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hudson, Dr Brian and Milligan, Professor Graeme
Authors: Milligan, G., Shimpukade, B., Ulven, T., and Hudson, B. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Chemical Reviews
Publisher:American Chemical Society
ISSN:0009-2665
ISSN (Online):1520-6890
Published Online:14 June 2016
Copyright Holders:Copyright © 2016 American Chemical Society
First Published:First published in Chemical Reviews 117(1): 67-110
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
448211Uncovering the pharmacology of the G-protein coupled reception GPR40Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/E019455/1RI NEUROSCIENCE & PSYCHOLOGY
659371Designer Receptor Exclusively Activated by Designer Drug' to define the role of short chain fatty acids in metabolic disease and inflammation (Fatty acid DREADD)Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/L027887/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
618921GPR120: a G protein-coupled receptor with the potential to regulate insulin secretion and inflammationGraeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/K019864/1RI MOLECULAR CELL & SYSTEMS BIOLOGY