BAR501 is an effective and specific GPBAR1 agonist (EC50: 1 μM).

In HEK293 cells overexpressing a CRE along with GPBAR1, BAR501 effectively transactivates GPBAR1 (EC50: 1 μM). In GLUTAg cells, BAR501 (10 μM) increases the mRNA expression of GLP-1 by 2.5 folds.

Pretreating rats for 6 days with BAR501 (15 mg/kg), the basal portal pressure reduces and the vasoconstriction activity of norepinephrine blunts. BAR501 attenuates the hepatic vasomotor activity induced by methoxamine and shear stress. In the CCl4 model, BAR501 exerts a direct vasodilatory activity. BAR501 (15 mg/kg) can reduce AST plasma levels and portal pressure. BAR501 attenuates endothelial dysfunction by regulating CSE expression/activity.

For GPBAR1 mediated transactivation, HEK-293T cells are plated at 10000 cells/well in a 24 well-plate and transfected with 200 ng of pGL4.29, a reporter vector containing a cAMP response element (CRE) that drives the transcription of the luciferase reporter gene luc2P, with 100 ng of pCMVSPORT6-human GPBAR1, and with 100 ng of pGL4.70. At 24 h post-transfection, HepG2 and HEK293T cells are incubated with 10 μM BAR501 for 18 h and luciferase activities are assayed and normalized against the Renilla activities[1].

Animal: C57BL6 miceAdministration: i.p., 500 μL/kg of CCl4 in an equal volume of paraffin oil twice a week for 9 weeks. CCL4 mice are randomized to receive BAR501 (15 mg/Kg daily by gavage) or vehicle (distilled water). Serum bilirubin, albumin, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase are measured by routine biochemical clinical chemistry[1].