Biochem/physiol Actions

TUG-891 is an orally active, potent and selective agonist for human long chain free fatty acid (FFA) receptor FFA4/GPR120 (pEC50 of receptor β-arrestin-2 recruitment = 7.36/FFA4 vs. 4.19/FFA1 HEK transfectants; pEC50 of calcium mobilization = 7.02/FFA4 vs. 5.30/FFA1 transfectants), while exhibiting no activity toward human short-chain FFA receptors FFA2/GPR43 and FFA3/GPR41. TUG-891 also exhibits potent partial agonist activity toward murine FFA4 (pEC50 = 7.77, 75% efficacy by β-arrestin-2 recruitment assay; pEC50 = 6.89 by calcium mobilization), albeit with a reduced selectivity over mFFA1 (pEC50 = 5.92 by β-arrestin-2 recruitment and 6.41 by by calcium mobilization). When administered via water intake (~20 mg/kg/day), TUG-891 is reported to reverse food intake increases and body weight gains among mice subjected to sleep fragmentation, and significantly attenuate visceral white adipose tissue inflammation as well as insulin resistance.

TUG-891, a GPR120 agonist helps to stimulate metabolic health by inducing mitochondrial respiration in brown fat. It is capable of enhancing lipid oxidation and decreasing fat mass in mice.