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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology*
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Cell Survival / drug effects
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Cinnamates / chemical synthesis*
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Cinnamates / chemistry
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Cinnamates / pharmacology*
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Diabetes Mellitus, Type 2 / drug therapy
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Glucagon-Like Peptide 1 / metabolism
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HEK293 Cells
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Humans
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Molecular Structure
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Phenylpropionates / chemical synthesis*
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Phenylpropionates / chemistry
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Phenylpropionates / pharmacology*
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Receptors, G-Protein-Coupled / agonists*
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Receptors, G-Protein-Coupled / metabolism
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Structure-Activity Relationship
Substances
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3-(4-((4-fluoro-4'-methyl-(1,1'-biphenyl)-2-yl)methoxy)phenyl)propanoic acid
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Biphenyl Compounds
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Cinnamates
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FFAR4 protein, human
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Phenylpropionates
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Receptors, G-Protein-Coupled
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Glucagon-Like Peptide 1