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Description
Overview
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.
Catalogue Number
504379
Brand Family
Calbiochem®
Synonyms
0X3, N-(3-Chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine, Hypoxia-Inducible Factor Inhibitor VI
References
References
Wu, D., et al. 2015. Nature in press. Scheuermann, T.H., et al. 2013. Nat. Chem. Biol.9, 271.
Wu, D., et al. 2015. Nature in press. Scheuermann, T.H., et al. 2013. Nat. Chem. Biol.9, 271.
Data Sheet
Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.
Revision
12-February-2015 JSW
Synonyms
0X3, N-(3-Chloro-5-fluorophenyl)-4-nitrobenzo[c][1,2,5]oxadiazol-5-amine, Hypoxia-Inducible Factor Inhibitor VI
Description
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.
Form
Yellow powder
Intert gas (Yes/No)
Packaged under inert gas
CAS number
1422955-31-4
Chemical formula
C₁₂H₆ClFN₄O₃
Structure formula
Purity
≥99% by HPLC
Solubility
DMSO (10 mg/ml). Use only fresh DMSO for reconstitution.
Storage
+2°C to +8°C
Protect from light
Do Not Freeze
Ok to freeze
Special Instructions
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Toxicity
Standard Handling
References
Wu, D., et al. 2015. Nature in press. Scheuermann, T.H., et al. 2013. Nat. Chem. Biol.9, 271.
