375240

HNF4 Antagonist, BI6015

The HNF4 Antagonist, BI6, also referenced under CAS 93987-29-2, controls the biological activity of HNF4.

• Synonym(s): HNF4 Antagonist, BI6015, 2-Methyl-1-(2-methyl-5-nitrophenylsulfonyl)-1H-benzo[d]imidazole, Hepatocyte Nuclear Factor4 Antagonist
• Empirical Formula (Hill Notation): C₁₅H₁₃N₃O₄S
• CAS Number: 93987-29-2
• Molecular Weight: 331.35
• UNSPSC Code: 12352200
• NACRES: NA.32
• MDL number: MFCD04406654
• Assay: ≥99% (HPLC)
• Form: powder
• Storage condition: OK to freeze, protect from light

Properties

• Quality Segment: 100
• assay: ≥99% (HPLC)
• form: powder
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: beige
• solubility: DMSO: 10 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: CC1=NC2=C(N1S(C3=CC([N+]([O-])=O)=CC=C3C)(=O)=O)C=CC=C2
• InChI: 1S/C15H13N3O4S/c1-10-7-8-12(18(19)20)9-15(10)23(21,22)17-11(2)16-13-5-3-4-6-14(13)17/h3-9H,1-2H3
• InChI key: ILVCPQPMRPHZSG-UHFFFAOYSA-N

Description

General description

A cell-permeable phenylsulfonylbenzimidazole compound that is shown to dock in the ligand-binding pocket of both HNF4α and HNF4γ via in silico structural analyses and antagonizes HNF4α DNA binding activity (by 93% after 10 µM overnight treatment of HepG2 cells), effectively inhibiting HNF4α-dependent cellular activities, including HNF4α mRNA transcription (by 62% in murine insulinoma MIN6 and 84% in human hepatoma HepG2 cultures after 5 h and 48 h 5 µM inhibitor treatment, respectively) and OTC (omithine transcarbamoylase) promoter transcription (by 85% & >95% in human HNF4α-transfected HepG2 & CV-1 cells, respectively; 48 hr 1 µM treatment). HNF4γ inhibition by BI6015 is also reported to indirectly lead to decreased binding of transactivators, E47 & PDX-1, to insulin promoter in T6PNE cells (48 h 5 µM treatment). Although BI6015 is found to exhibit cancer-selective cytotoxicity toward a panel of 58 human cancer cells and Hep3B-Luc (Effective conc. 1 to 10 µM), but not primary murine hepatocytes, it does cause hepatic steatosis both in vitro (primary murine hepatocytes; 5 µM for 3 days) and in mice in vivo (10 to 30 mg/kg/day for 5 days via i.p.) and is effectively metabolized by liver enzymes, limiting its in vivo efficacy in treating human Hep3B-derived liver tumor in mice. BI6015 also inhibits Human CYP450 2C19 and rat L-type calcium channel (by 94% and 83%, respectively, at 10 µM), but not PPARγ or a panel of 41 receptors/enzymes of human, mouse, and rat origin.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
HNFα & γ

Reversible: yes

Packaging

Packaged under inert gas

Other Notes

Kiselyuk, A., et al. 2012. Chem. Biol.19, 806.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk: WGK 2
• flash_point_f: Not applicable
• flash_point_c: Not applicable