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Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines

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Free Fatty Acid Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 236))

Abstract

The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans. Expression profiling, the phenotyping of FFA receptor knockout mice, and the results of studies exploring the effects of these ligands in rodents have uncovered a number of indications where engagement of one or a combination of FFA receptors might provide some clinical benefit in areas including diabetes, inflammatory bowel syndrome, Alzheimer’s, pain, and cancer. In this chapter, we will review the clinical potential of modulating FFA receptors based on preclinical and in some cases clinical studies with synthetic ligands. In particular, key aspects and challenges associated with small-molecule ligand identification and FFA receptor pharmacology will be addressed with a view of the hurdles that need to be overcome to fully understand the potential of the receptors as therapeutic targets.

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Acknowledgments

We thank Stephen Jenkinson and David Polidori for critical reading of the manuscript.

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  1. MedImmune, LLC, Gaithersburg, MD, 20878, USA

    Arthur T. Suckow

  2. Epigen Biosciences, 10225 Barnes Canyon Rd, San Diego, CA, 92121, USA

    Celia P. Briscoe

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  1. Inst. Molecular, Cell & Systems Biology, University of Glasgow, Glasgow, Lanarkshire, United Kingdom

    Graeme Milligan

  2. Dep of Applied Biological Science, Tokyo Univ of Agriculture and Technology, Fuchu-shi, Tokyo, Japan

    Ikuo Kimura

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Suckow, A.T., Briscoe, C.P. (2016). Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines. In: Milligan, G., Kimura, I. (eds) Free Fatty Acid Receptors. Handbook of Experimental Pharmacology, vol 236. Springer, Cham. https://doi.org/10.1007/164_2016_45

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