IOX2 IOX2;2-(1-benzyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxaMido)acetic acid;N-[[4-Hydroxy-2-oxo-1-(phenylmethyl)-1,2-dihydro-3-quinolinyl]carbonyl]glycine;Glycine, N-[[1,2-dihydro-4-hydroxy-2-oxo- 931398-72-0
IOX2 is a selective inhibitor of the Hypoxia Inducible Factor (HIF) Prolyl-Hydroxylases (PHD); active in cells with IC50 value of 21 nM for PHD2/ELGN-1 and no inhibition at FIH (20uM).
IC50 value: 21 nM
Target: HIF Prolyl-Hydroxylases
Hypoxia Inducible Factor (HIF) is regulated by the hydroxylation of prolyl residues in oxygen-dependent degradation domains in the HIF-1α subunit, which mark it for degradation by the proteosome. HIF prolyl hydroxylation is catalyzed by prolyl hydroxylase domain enzymes (PHD1, 2, and 3), members of the Fe(II) and 2-oxoglutarate (2OG) oxygenase family. They require dioxygen as a cosubstrate, thus acting as the hypoxia-sensing component of the HIF system. The activity of PHD is suppressed by hypoxia, increasing both the abundance and activity of the HIF transcriptional complex. IOX2 potently inhibits PHD2 (IC50 value of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM.
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