HNF4 Antagonist, BI6015-CAS 93987-29-2-Calbiochem

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一般描述

A cell-permeable phenylsulfonylbenzimidazole compound that is shown to dock in the ligand-binding pocket of both HNF4α and HNF4γ viain silicostructural analyses and antagonizes HNF4α DNA binding activity (by 93% after 10 ?M 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 ?M inhibitor treatment, respectively) and OTC (omithine transcarbamoylase) promoter transcription (by 85% & >95% in human HNF4α-transfected HepG2 & CV-1 cells, respectively; 48 hr 1 ?M 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 ?M 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 ?M), but not primary murine hepatocytes, it does cause hepatic steatosis bothin vitro(primary murine hepatocytes; 5 ?M for 3 days) and in micein vivo(10 to 30 mg/kg/day for 5 days via i.p.) and is effectively metabolized by liver enzymes, limiting itsin vivoefficacy 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 ?M), 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 ?M overnight), effectively inhibiting HNF4α-dependent cellular activities (Effective conc. 1 to 5 ?M). HNF4γ inhibition by BI6015 can also lead to decreased insulin promoter binding by transactivators E47 & PDX-1 in T6PNE cells (5 ?M 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 ?M), but not primary murine hepatocytes, it does cause hepatic steatosis bothin vitroand in micein 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 ?M), but not PPARγ or a panel of 41 receptors/enzymes of human, mouse, and rat origin.

包装

25 mg in Glass bottle
Packaged under inert gas

生化/生理作用

Cell permeable: yes
Reversible: yes
Primary Target
HNFα & γ

警告

Toxicity: Standard Handling (A)

其他说明

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

法律信息

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

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