Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor transcription factor that controls the expression of many genes including those involved in glucose and lipid homeostasis and maintenance of epithelial differentiation. BI6015 is a small molecule antagonist of Hepatocyte nuclear factor 4α (HNF4α) that has been shown to repress the expression of known HNF4α target genes. At concentrations up to 20 μM, BI6015 has been shown to reduce endogenous insulin gene expression by as much as 50-fold in T6PNE cells. The hepatocytes from livers of mice injected with 10 and 30 mg/kg BI6015 exhibit marked, dose-dependent fat accumulation (steatosis). Additionally, at a daily dose of 30 mg/kg, BI6015 induces apoptosis in a human hepatocellular carcinoma mouse model.
