IOX1
2-oxoglutarate (2OG) and other Fe(II)-dependent oxygenases are an important family of enzymes with roles in collagen biosynthesis, lipid metabolism, nucleic acid repair and modification, histone demethylation, and hypoxic sensing.{18346,20944,18060} Impaired 2OG oxygenase activity is linked to the cellular hypoxic response and various diseases including cancer.{20945} Iron-chelators, Co(II) ions, and 2OG analogues such as pyridine-2,4-dicarboxylate and N-oxalylglycine have been used as non-selective inhibitors of 2OG oxygenases.{18060,20945,20943} However, they require administration as pro-drug diester derivatives. IOX1 is a broad-spectrum inhibitor of 2OG oxygenases that does not require application in a pro-drug formulation. IOX1 inhibits JMJD2A, JMJD2E and the 2OG oxygenases PHF8, PHD2, and FIH with IC50 values of 1.7, 2.4, 13.3, 14.3, and 20.5 ?M, respectively.{20945} IOX1 inhibits H3K9me3 demethylation by JMJD2A in HeLa cells with an IC50 value of 87 ?M.{20945} See the Structural Genomics Consortium (SGC) website for more information.
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