IC50: 6 nM

TUG-770 is a potent free fatty acid receptor 1 (FFA1/GPR40) agonist. Free fatty acid receptor 1 (FFA1 or GPR40) enhances the glucose-stimulated insulin secretion from pancreatic β-cells and attracts high interest as a new target for the treatment of type 2 diabetes.

In vitro: TUG-770 showed a pronounced increase in potency on FFA1 with EC50 = 6 nM and 150-fold selectivity over FFA4. TUG-770 showed a high selectivity over FFA2, FFA3, PPARγ, and 54 diverse transporters, receptors, and enzymes. In the rat INS-1E cell line, TUG-770 caused significantly increased insulin secretion at high glucose concentration and, as expected, no effect at low glucose concentration [1].

In vivo: Pharmacokinetic studies of TUG-770 in mice showed a fast oral absorption, higher plasma concentration, a longer half-life, lower clearance, and increased bioavailability. No adverse effects were seen in mice after four weeks of daily oral treatment of 20 mg/kg and acute treatment in doses up to 250 mg/kg. In vivo examination of TUG-770 in an acute intraperitoneal glucose tolerance test in normal mice showed a good dose-dependent response with maximal reduction in glucose level reached at 50 mg/kg. The followed chronic oral glucose tolerance test study in DIO mice showed that TUG-770 was more effective than its analog. Further evaluation of TUG-770 in rats confirmed a significant glucose lowering effect for the high doses [1].

Clinical trial: N/A

Reference:
[1] Christiansen E,Hansen SV,Urban C,Hudson BD,Wargent ET,Grundmann M,Jenkins L,Zaibi M,Stocker CJ,Ullrich S,Kostenis E,Kassack MU,Milligan G,Cawthorne MA,Ulven T.  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.