title: Discovery of a potent and selective GPR120 agonist.
abstract: GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist.
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
authors.forename: Bharat
authors.initials: B
authors.lastname: Shimpukade
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hudson
authors.forename: Christine Kiel
authors.initials: CK
authors.lastname: Hovgaard
authors.forename: Graeme
authors.initials: G
authors.lastname: Milligan
authors.forename: Trond
authors.initials: T
authors.lastname: Ulven
mesh_terms: D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C585065:3-(4-((4-fluoro-4'-methyl-(1,1'-biphenyl)-2-yl)methoxy)phenyl)propanoic acid; D001713:Biphenyl Compounds; D002934:Cinnamates; C519853:FFAR4 protein, human; D010666:Phenylpropionates; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1