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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. BIM5078 is an HNF4α antagonist that can repress the expression of known HNF4α target genes, inhibiting endogenous insulin expression in T6PNE cells with an IC₅₀ value of 930 nM. BIM5078 binds directly to the ligand binding pocket of HNF4α with an EC₅₀ value of 11.9 nM. However, BIM5078 has unfavorable pharmacokinetic properties including low plasma and microsomal stability (8% remaining after 3 hours and 32% after 1.25 hours, respectively), high binding to plasma proteins (98% bound after 4 hours), and low solubility (0.17 mg/ml after 18 hours). BI6015 is a structural analog of BIM5078 developed for more favorable pharmacokinetics.

BIM5078 is a hepatocyte nuclear factor 4α (HNF4α) antagonist that can inhibit the expression of known HNF4α target genes. BIM5078 represses insulin promoter activity through HNF4α antagonism. BIM5078 can be used for the research of cancer and diabetes[1].

[1] Kiselyuk A, et al. HNF4α antagonists discovered by a high-throughput screen for modulators of the human insulin promoter. Chem Biol. 2012 Jul 27;19(7):806-18. DOI:10.1016/j.chembiol.2012.05.014