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Selective Inhibitors of AlkB Family of Nucleic Acid Demethylases.

The α-ketoglutarate-dependent (AlkB) superfamily of FeII/2-oxoglutarate (2-OG) -dependent dioxygenases consists of a unique class of nucleic acid repair enzymes which reversibly remove alkyl substituents from nucleobases through oxidative dealkylation. Recent studies have verified the involvement of AlkB dioxygenases in a variety of human diseases. However, the development of small organic molecules that can function as enzyme inhibitors to block the action of oxidative dealkylation is still in its infancy. These purposeful chemical motifs, if capable of influencing the dealkylation activity, would have a potential clinical value by controlling genetic information expression. In this Perspective, we will summarize some of the most updated inhibitors of AlkB family demethylases, and hope to provide a thought for the follow-up screening optimization.