ArticleMolecular pharmacology2013
The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93 citing papers in PubMed, 198 citations in OpenAlex.
- Decoy bypass for appetite suppression in obese adults: role of synergistic nutrient sensing receptors GPR84 and FFAR4 on colonic endocrine cells.Gut · 2022 · on this mapTrial
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- The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026Review
- The Multifaceted Roles of GPR120 in Central Nervous System Disorders: Mechanistic Insights and Therapeutic Implications.Molecular neurobiology · 2026Review
- Agonism of FFA4/GPR120 activates tyrosine hydroxylase and confers neuroprotection from 6-OHDA-induced cytotoxicity in PC12 cells and in a rat 6-OHDA model of Parkinson's disease.Biochemical pharmacology · 2026Article
- Intracrine FFA4 signaling controls lipolysis at lipid droplets.Nature chemical biology · 2026Article
- FFAR4 drives stem cell fate toward lipid- and iron-storing enterocytes protecting human enteroids from ferroptosis.Stem cell research & therapy · 2025Article
- Review
- FFAR4-mediated IL-6 release from islet macrophages promotes insulin secretion and is compromised in type-2 diabetes.Nature communications · 2025Article
- Potential Therapeutic Exploitation of G Protein-Coupled Receptor 120 (GPR120/FFAR4) Signaling in Obesity-Related Metabolic Disorders.International journal of molecular sciences · 2025Review
- Biased agonism at free-fatty acid receptor-4 (FFA4/GPR120).Pharmacology & therapeutics · 2025Review
- Postoral receptors and alimentary taste: implications for energy intake and appetite.Chemical senses · 2025Review
- TNFα-CXCR1/2 partners in crime in insulin resistance conditions.Cell death discovery · 2024Article
- Novel Phenoxyalkanoic Acid Derivatives as Free Fatty Acid Receptor 4 Agonists for Treating Type 2 Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.International journal of molecular sciences · 2024Review
- GPCRs involved in metabolic diseases: pharmacotherapeutic development updates.Acta pharmacologica Sinica · 2024Review
- Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity.Bone research · 2024Article
- Structural basis for the ligand recognition and signaling of free fatty acid receptors.Science advances · 2024Article
- Free fatty acid receptors beyond fatty acids: A computational journey to explore peptides as possible binders of GPR120.Current research in food science · 2024Article
- Signaling pathways in cancer metabolism: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
TUG-891 [3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic acid] was recently described as a potent and selective agonist for the long chain free fatty acid (LCFA) receptor 4 (FFA4; previously G protein-coupled receptor 120, or GPR120). Herein, we have used TUG-891 to further define the function of FFA4 and used this compound in proof of principle studies to indicate the therapeutic potential of this receptor. TUG-891 displayed similar signaling properties to the LCFA α-linolenic acid at human FFA4 across various assay end points, including stimulation of Ca²⁺ mobilization, β-arrestin-1 and β-arrestin-2 recruitment, and extracellular signal-regulated kinase phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. While these latter events were associated with desensitization of the FFA4 signaling response, removal of TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and resensitization of the FFA4 Ca²⁺ signaling response. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species. Pharmacologic dissection of responses to TUG-891 in model murine cell systems indicated that activation of FFA4 was able to mimic many potentially beneficial therapeutic properties previously reported for LCFAs, including stimulating glucagon-like peptide-1 secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1 adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7 macrophages, which suggests promise for FFA4 as a therapeutic target for type 2 diabetes and obesity. Together, these results demonstrate both potential but also significant challenges that still need to be overcome to therapeutically target FFA4.
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