RG-239 is an orally active TGR5 agonist with an EC50 of 120 nM, significantly more potent than Betulinic acid (EC50= 1.04 μM). It exhibits much higher selectivity for TGR5 over FXRα. The compound enhances mitochondrial activity in adipocytes and promotes neurite outgrowth at higher concentrations. Additionally, RG-239 inhibits LPS-induced iNOS expression and nitrite production in Raw264.7 cells and microglia. RG-239 is applicable for research related to type 2 diabetes.

RG-239 (Compound 18 dia 2) at a concentration of 10 μM enhances mitochondrial activity in adipocytes, demonstrated by increased cytochrome c oxidase activity in 3T3L1 fat cells. At 1 μM, RG-239 induces neurite outgrowth to 9.5 μm, which is significantly less effective than Retinoic acid (RA). However, at 10 μM, it induces a median neurite length of 37.0 μm, comparable to the effect of Deoxycholic acid (DCA) in NSC-34 cells. Additionally, RG-239 at 2 μM for 24 hours inhibits iNOS expression and nitrite production in LPS-induced Raw264.7 and microglial cells.

RG-239 (Compound 18 dia 2), administered orally at 30 mg/kg/day for 3 weeks, can reduce plasma glucose levels in obese mice induced by a 10-week high-fat diet (60% of calories from fat). Additionally, a dosage of RG-239 at 10 mg/kg/day for 2 weeks can decrease the expression of inflammatory genes Tnfα, IL-6, and IL-1β in the liver of B6J mice subjected to the same high-fat diet.