A cell-permeable benzoxadiazolamine that prevents HIF-2alpha-HIF-beta/ARNT heterodimeration by perturbing HIF-2alpha Per-ARNT-Sim/PAS-B domain surface beta-sheet conformation via a 1:1 stoichiometric binding (KD = 81nM), while exhibiting no affinity toward HIF-1alphaPAS-B domain. Shown to be metabolically stable and non-cytotoxic in cultures and selectively inhibit hypoxia-induced HIF-2a DNA binding and HIF-2alpha-dependent EPO mRNA upregulation (1 to10uM for 6-12h), but not HIF-1alpha DNA binding or HIF-1alpha-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-1alpha & HIF-2alpha.
Storage and Stability:May be stored at 4°C. For long-term storage, aliquot and store at 4°C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.