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Overview
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Background
BI 6015 is an antagonist of hepatocyte nuclear factor 4α [1].
Hepatocyte nuclear factor 4α (HNF4α) is a nuclear receptor and regulates gene expression in enterocytes, hepatocytes and pancreatic β cells [1].
BI 6015 is a HNF4α antagonist. BI6015 inhibited the insulin promoter. In T6PNE cells, BI6015 reduced the expression of endogenous insulin by 50-fold. In MIN6 and HepG2 cells, BI6015 inhibited the expression of HNF4α. Also, BI6015 changed HNF4α protease sensitivity [1]. In T6PNE cells, BI 6015 reduced the levels of longer chain acylcarnitines (C18, C18:1, C16, and C14) and increased acetylcarnitine, which suggested that BI 6015 increased fatty acid oxidation. In the human hepatoma cell line Hep3B, BI 6015 exhibited cytotoxic activity [1].
In mice, BI6015 (30 mg/kg) induced a loss of HNF4α protein in the liver, but not in the kidney and intestine. Also, BI6015 caused fat accumulation and steatosis and vesicular changes in a dose-dependent way [1].
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