产品描述

BAR501 is a potent and selective agonist of GPBAR1 with an EC50 of 1 μM.

靶点（IC50 & Targe）

GPBAR1,1μM

GPCR19 agonist

体外研究

BAR501 is a selective GPBAR1 agonist devoid of FXR agonistic activity. It effectively transactivates GPBAR1 in HEK293 cells overexpressing a CRE along with GPBAR1, with an EC50 of 1 μM. Exposure of GLUTAg cells to BAR501 (10 μM) increases the expression of GLP-1 mRNA by 2.5 folds[1].

体内研究

Pretreating rats for 6 days with BAR501, 15 mg/kg, reduces basal portal pressure and blunts the vasoconstriction activity of norepinephrine. Pretreatment with BAR501 attenuates the hepatic vasomotor activity induced by shear stress and methoxamine. Administration of BAR501 exerts a direct vasodilatory activity in the CCl4 model. Treating mice with BAR501 at the dose of 15 mg/Kg reduces portal pressure and AST plasma levels. BAR501 attenuates endothelial dysfunction by regulating CSE expression/activity[1].

细胞实验

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].MCE has not independently confirmed the accuracy of these methods. They are for reference only.

动物实验

Mice: C57BL6 mice are administered i.p. 500 μL/Kg body weight 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 minotransferase and alkaline phosphatase are measured by routine biochemical clinical chemistry[1].MCE has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献

[1]. Renga B, et al. Reversal of Endothelial Dysfunction by GPBAR1 Agonism in Portal Hypertension Involves a AKT/FOXOA1 Dependent Regulation of H2S Generation and Endothelin-1. PLoS One. 2015 Nov 5;10(11):e0141082.