A cell-permeable benzimidazolopyrazole compound that acts as an active-site binding, iron insensitive, 2-oxoglutarate competitive, reversible and potent inhibitor of PHD1, 2 and 3 isozymes (pKi=7.91, 7.29 and 7.65, respectively). Displays >100-fold selectivity over FIH (factor inhibiting hydroxylase; pIC50 ~4) and minimal affinity towards a panel of receptors, enzymes and kinases. Shown to elevate HIF-1a levels in Hep3B cells and stimulate erythropoietin secretion in mice, and reverse inflammation-induced anemia in rats (100uM/kg). Shown to inhibit malate dehydrogenase 2 (MDH2) activity and suppress mitochondrial respiration.
Synonyms: 1-(5-Chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid, HIF Prolyl Hydroxylase Inhibitor II
Molecular Formula:C₁₂H₆ClF₃N₄O₃
Molecular Weight:346.7
Solubility:DMSO (100mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
