BI-6015

BI-6015 is a hepatocyte nuclear factor 4α (HNF4α) antagonist and a meta-substituted positional isomer of CAY10803 (Item No. 12032)¹ It reduces the expression of HNF4α in T6PNE and MIN6 cells at 2.5 and 5 µM. It also reduces the expression of a reporter driven by the HNF4α-responsive ornithine transcarbamylase (OTC) promoter in reporter assays using HepG2 and CV-1 cells. BI-6015 reduces HNF4α binding to DNA in HepG2 cells at 10 and 20 µM and induces hepatic steatosis in primary mouse hepatocytes at 5 µM. It reduces hepatic HNF4α levels and induces steatosis in the liver, but not the intestine or kidney, in mice. BI-6015 (20 mg/kg per day) also prevents increases in serum aspartate aminotransferase (AST), alanine transaminase (ALT), bilirubin, and bile acid levels in a mouse model of parenteral nutrition-associated cholestasis (PNAC).² It induces cytotoxicity in Hep3B hepatocellular carcinoma (HCC) cells and apoptosis in tumors in an orthotopic Hep3B mouse xenograft model.¹

WARNING This product is not for human or veterinary use.

1. Chao, S.H., Fujinaga, K., Marion, J.E., et al. Flavopiridol inhibits P-TEFb and blocks HIV-1 replication. The Journal of Biological Chemisty 275(37), 28345-28348 (2000).

2. Ghosh, S., Devereaux, M.W., Orlicky, D.J., et al. Pharmacologic inhibition of HNF4α prevents parenteral nutrition associated cholestasis in mice. Sci. Rep. 13(1), 7752 (2023).