375240

HNF4 Antagonist, BI6015

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

• Sinonimo/i: HNF4 Antagonist, BI6015, 2-Methyl-1-(2-methyl-5-nitrophenylsulfonyl)-1H-benzo[d]imidazole, Hepatocyte Nuclear Factor4 Antagonist
• Formula empirica (notazione di Hill): C₁₅H₁₃N₃O₄S
• Numero CAS: 93987-29-2
• Peso molecolare: 331.35
• Numero MDL: MFCD04406654
• Codice UNSPSC: 12352200
• NACRES: NA.32

Proprietà

• Livello qualitativo: 100
• Saggio: ≥99% (HPLC)
• Forma fisica: powder
• Produttore/marchio commerciale: Calbiochem^®
• Condizioni di stoccaggio: OK to freeze; protect from light
• Colore: beige
• Solubilità: DMSO: 10 mg/mL
• Condizioni di spedizione: ambient
• Temperatura di conservazione: 2-8°C
• Stringa SMILE: 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; ILVCPQPMRPHZSG-UHFFFAOYSA-N

Descrizione

Descrizione generale

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.

A cell-permeable phenylsulfonylbenzimidazole that is shown to dock in the ligand-binding pocket of both HNF4α and HNF4γ and antagonize HNF4α DNA binding activity in HepG2 cells (by 93%; 10 µM overnight), effectively inhibiting HNF4α-dependent cellular activities (Effective conc. 1 to 5 µM). HNF4γ inhibition by BI6015 can also lead to decreased insulin promoter binding by transactivators E47 & PDX-1 in T6PNE cells (5 µM 48 h). 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 and in mice in vivo, limiting its use in animal studies. 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.

Azioni biochim/fisiol

Cell permeable: yes

Primary Target
HNFα & γ

Reversible: yes

Confezionamento

Packaged under inert gas

Attenzione

Toxicity: Standard Handling (A)

Altre note

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

Note legali

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

Informazioni sulla sicurezza

• Codice della classe di stoccaggio: 11 - Combustible Solids
• Classe di pericolosità dell'acqua (WGK): WGK 2
• Punto d’infiammabilità (°F): Not applicable
• Punto d’infiammabilità (°C): Not applicable