TUG-770

• CAT Number: I001537
• CAS Number: 1402601-82-4
• Molecular Formula: C19H14FNO2
• Molecular Weight: 307.32
• Purity: ≥95%
• Synonyms: 3-[4-[2-[2-(cyanomethyl)phenyl]ethynyl]-2-fluorophenyl]propanoic acid
• InChI: InChI=1S/C19H14FNO2/c20-18-13-14(6-8-17(18)9-10-19(22)23)5-7-15-3-1-2-4-16(15)11-12-21/h1-4,6,8,13H,9-11H2,(H,22,23)
• InChIKey: KIZUBVPJNPVIIN-UHFFFAOYSA-N
• SMILES: C1=CC=C(C(=C1)CC#N)C#CC2=CC(=C(C=C2)CCC(=O)O)F

TUG-770 is a potent, selective and orally active GPR40/FFA1 agonist with an EC50 of 6 nM for human FFA1. TUG-770 shows a high selectivity for FFA1 over FFA2, FFA3, FFA4, PPARγ, other receptors, transporters, and enzymes. TUG-770 can be uesd for type 2 diabetes research[1]. TUG-770 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
TUG-770 (Compound 22) displays excellent physicochemical and in vitro ADME properties, with good aqueous solubility, good chemical stability, low lipophilicity, and decreased plasma protein binding (PPB). TUG-770 shows excellent stability toward human liver microsomes (HLM), and good permeability in the Caco-2 cell assay[1].
TUG-770 exhibits lower potency on the rodent orthologs (mFFA1, pEC50 = 6.83; rFFA1, pEC50 = 6.49)[1].
In the rat INS-1E cell line, TUG-770 significantly increases insulin secretion (10.75% of total content with 10 μM 22 vs 8.74 with vehicle) at high glucose concentration (12.4 mM) and, no effect (4.14% of total content with 10 μM 22 vs 4.02 with vehicle) at low glucose concentration (2.8 mM)[1].
TUG-770 (Compound 22; 20 mg/kg; oral administration; daily; for 28 days) treatment significantly improves glucose tolerance, and has no effect on food intake, body weight, body composition or plasma leptin concentration. TUG-770 also significantly improves the insulin sensitivity index (plasma glucose x plasma insulin) [1].

Reference

[1]. Christiansen E, et al. Discovery of TUG-770: A Highly Potent Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonist for Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2013 May 9;4(5):441-445.
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