1000403-03-1

INT-767 is a G-protein coupled/Farnesoid X-activated receptor agonist potentially for the treatment of hepatic fibrosis. INT-767 significantly improved serum liver enzymes, hepatic inflammation, and biliary fibrosis in Mdr2(-/-) mice. INT-767 significantly induced bile flow and biliary HCO?3- output, as well as gene expression of carbonic anhydrase 14, an important enzyme able to enhance HCO?3- transport, in an Fxr-dependent manner. In addition, INT-767 dramatically reduced bile acid synthesis via the induction of ileal Fgf15 and hepatic Shp gene expression, thus resulting in significantly reduced biliary bile acid output in Mdr2(-/-) mice.

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