TUG-770

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, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. IC50 & Target: EC50: 6 nM (Human GPR40/FFA1)^[1] In Vitro: 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]. In Vivo: 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].