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5.04379

Sigma-Aldrich

HIF Inhibitor VII

Synonym(s):

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

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About This Item

Empirical Formula (Hill Notation):
C12H6ClFN4O3
CAS Number:
1422955-31-4
Molecular Weight:
308.65
UNSPSC Code:
12352200
NACRES:
NA.77

assay

≥99% (HPLC)

Quality Level

100

form

powder

manufacturer/tradename

Calbiochem®

storage condition

OK to freeze
protect from light

color

yellow

solubility

DMSO: 10 mg/mL

storage temp.

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

InChI key

CDQUJZKBRAFWNG-UHFFFAOYSA-N

General description

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 (KD = 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 (t1/2 = 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 (KD = 81 nM), while exhibiting no affinity toward HIF-1α PAS-B domain (KD >>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.

Biochem/physiol Actions

Cell permeable: yes
Primary Target
HIF-2α
Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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.

Other Notes

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

Legal Information

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

Storage Class

11 - Combustible Solids

wgk_germany

WGK 3

Certificates of Analysis (COA)

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