The potential of 2-oxoglutarate oxygenases acting on nucleic acids as therapeutic targets

Human 2-oxoglutarate dependent oxygenases, including histone demethylases and hypoxia inducible transcription factor hydroxylases, catalyze posttranslational modifications and are being pursued as targets for cancer, anemia and ischemic and inflammatory diseases. Nucleic acid-modifying 2OG oxygenases (NAOX) catalyze 5-methylcytosine oxidation, tRNA hydroxylation, and the dealkylation of nucleobases; NAOX have roles in cell differentiation, nucleic acid repair and metabolic regulation. We review recent functional and pathophysiological studies on NAOX and discuss emerging therapeutic opportunities with the aim of stimulating further studies on NAOX inhibition.