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About This Item
Empirical Formula (Hill Notation):
C12H6ClFN4O3
CAS Number:
Molecular Weight:
308.65
MDL number:
UNSPSC Code:
12352200
NACRES:
NA.77
Assay
≥99% (HPLC)
Quality Level
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
SMILES string
Fc1cc(cc(c1)Nc2c(c3n[o]nc3cc2)[N+](=O)[O-])Cl
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
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.
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 Code
11 - Combustible Solids
WGK
WGK 3
Certificates of Analysis (COA)
Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.
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