5.04379

HIF Inhibitor VII

• Sinónimos: HIF Inhibitor VII, 0X3, Hypoxia-Inducible Factor Inhibitor VI, N-(3-Chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine, 0X3, N-(3-Chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine, Hypoxia-Inducible Factor Inhibitor VI, 504379
• Fórmula empírica (notación de Hill): C₁₂H₆ClFN₄O₃
• Número de CAS: 1422955-31-4
• Peso molecular: 308.65
• Código UNSPSC: 12352200
• NACRES: NA.77

Propiedades

• Análisis: ≥99% (HPLC)
• Nivel de calidad: 100
• formulario: powder
• fabricante / nombre comercial: Calbiochem^®
• condiciones de almacenamiento: OK to freeze; protect from light
• color: yellow
• solubilidad: DMSO: 10 mg/mL
• temp. de almacenamiento: 2-8°C
• InChI: 1S/C12H6ClFN4O3/c13-6-3-7(14)5-8(4-6)15-10-2-1-9-11(17-21-16-9)12(10)18(19)20/h1-5,15H
• Clave InChI: CDQUJZKBRAFWNG-UHFFFAOYSA-N

Descripción

Descripción general

A cell-permeable benzoxadiazolamine that prevents HIF-2α-HIF-β/ARNT heterodimeration by perturbing HIF-2α Per-ARNT-Sim/PAS-B domain surface β-sheet conformation via a 1:1 stoichiometric binding (K_D = 81 nM), while exhibiting no affinity toward HIF-1αPAS-B domain. Shown to be metabolically stable and non-cytotoxic in cultures and selectively inhibit hypoxia-induced HIF-2α DNA binding and HIF-2α-dependent EPO mRNA upregulation (1 to10 µM for 6 to 12 h), but not HIF-1α DNA binding or HIF-1α-dependent PGK1 mRNA upregulation, in Hep3B cells. Unlike HIF Inhibitors I-VI, this compound does not affect the cellular protein or mRNA levels of HIF-1α & HIF-2α.

A cell-permeable, metabolically stable (t_1/2 = 14 h in 786-0 cultures; no metabolization up to 24 h in medium alone), non-cytotoxic (up to 30 µM & 24 h in 786-0 and Hep3B cultures) benzoxadiazolamine that prevents HIF-2α-HIF-β/ARNT (aryl hydrocarbon receptor nuclear translocator) heterodimeration by perturbing HIF-2α Per-ARNT-Sim/PAS-B domain surface β-sheet conformation via a 1:1 stoichiometric binding to HIF-2α PAS-B internal cavity (K_D = 81 nM), while exhibiting no affinity toward HIF-1α PAS-B domain (K_D >>5 µM). Shown to inhibit nuclear HIF-2α-ARNT, but not HIF-1α-ARNT, association in hypoxic Hep3B cells in a dose-dependent manner (0.1 to 10 µM) and selectively decrease hypoxia-induced HIF-2α DNA binding and HIF-2α-dependent EPO mRNA upregulation (% inhibition/time/dose = 60%/6 h/1 µM, 90%/6 h/10 µM, 45%/12 h/1 µM, 93%/12 h/10 µM), displaying little effect toward HIF-1α DNA binding or HIF-1α-dependent PGK1 mRNA upregulation. Unlike HIF Inhibitors I-VI, this compound does not affect the cellular protein or mRNA levels of HIF-1α & HIF-2α.

Acciones bioquímicas o fisiológicas

Cell permeable: yes

Primary Target
HIF-2α

Reversible: yes

Envase

Packaged under inert gas

Advertencia

Toxicity: Standard Handling (A)

Reconstitución

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Otras notas

Wu, D., et al. 2015. Nature in press.
Scheuermann, T.H., et al. 2013. Nat. Chem. Biol.9, 271.

Información legal

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

Información de seguridad

• Código de clase de almacenamiento: 11 - Combustible Solids
• Clase de riesgo para el agua (WGK): WGK 3