TUG-891

• CAT Number: I001441
• CAS Number: 1374516-07-0
• Molecular Formula: C23H21FO3
• Molecular Weight: 364.4
• Purity: ≥95%
• Synonyms: 3-(4-((4-fluoro-4/’-methyl-[1,1/’-biphenyl]-2-yl)methoxy)phenyl)propanoic acid
• Target: Free Fatty Acid Receptor
• Solubility: 10 mM in DMSO
• Storage: Store at RT
• InChIKey: LPGBXHWIQNZEJB-UHFFFAOYSA-N

TUG-891 (CAT: I001441) is a potent and selective agonist for the long-chain free fatty acid (LCFA) receptor 4. LCFA receptor 4, also known as G protein-coupled receptor 120 (GPR120), is primarily expressed in adipose tissue and the gastrointestinal tract. By selectively activating this receptor, TUG-891 can modulate various metabolic processes, including regulation of insulin secretion, enhancement of glucose uptake, and promotion of lipid metabolism. The specific activation of LCFA receptor 4 by TUG-891 holds potential for therapeutic applications in metabolic disorders such as type 2 diabetes, obesity, and cardiovascular diseases.

Reference

1:Mol Pharmacol. 2013 Nov;84(5):710-25. doi: 10.1124/mol.113.087783. Epub 2013 Aug 26. 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.Hudson BD,Shimpukade B,Mackenzie AE,Butcher AJ,Pediani JD,Christiansen E,Heathcote H,Tobin AB,Ulven T,Milligan G, PMID: 23979972 PMCID: PMC3807074 DOI: 10.1124/mol.113.087783 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.