tcsc3199 INT-777

INT-777 is a potent TGR5 agonist with an EC₅₀ of 0.82 μM.

IC50 & Target: EC50: 0.82 μM (TGR5)^[1]

In Vitro: INT-777 is a novel potent and selective TGR5 agonist with remarkable in vivo activity^[1]. INT-777 (3 μM) increases ATP production in the human enteroendocrine cell line NCI-H716 in a cAMP-dependent manner^[2]. INT-777 (10 μM) lowers Isc and increases TEER when added on the serosal side of seromuscular stripped distal colon segments. INT-777 effect on basal secretion is reduced in neuron-free and TTX-treated mucosal-submucosal preparations^[3].

In Vivo: INT-777 (1 μM/min/kg, p.o.) has a potent choleretic effect, prevents carboxyl CoA activation and subsequent conjugation, thereby favoring its cholehepatic shunt pathway with a ductular absorption and a potent choleretic effect in HF-fed TGR5-Tg male mice^[1]. INT-777 (30 mg/kg/day, p.o.) increases energy expenditure and reduces hepatic steatosis and obesity upon high fat feeding, and improves insulin sensitivity, in TGR5-Tg mice^[2].