ALKBH6 Inhibitors

ALKBH6 inhibitors encompass a range of compounds that can indirectly affect the enzyme's activity by targeting the cofactors and substrates necessary for its function or influencing global methylation levels. These compounds are not inhibitors of ALKBH6 in the traditional sense; rather, they interfere with the enzyme's activity by altering its biochemical environment. Compounds like Methylstat and ML324 are known to target other enzymes involved in methylation, but their effect on ALKBH6 could be inferred given the enzyme's role in processing methylated substrates. By modulating the methylation landscape within the cell, these compounds can indirectly impact the function of ALKBH6.

IOX1, Succinate, Dimethyloxalylglycine (DMOG), N-Oxalylglycine (NOG), and Pyridine-2,4-dicarboxylate are inhibitors of 2-oxoglutarate-dependent dioxygenases. These compounds compete with or mimic the enzyme's cofactors, reducing ALKBH6 activity by limiting its access to necessary substrates. This class of inhibitors demonstrates the strategy of targeting an enzyme's dependence on cofactors for indirect inhibition. Ciclopirox and Deferiprone function as iron chelators, and since ALKBH6, like other AlkB family members, is a Fe(II)/2-oxoglutarate-dependent enzyme, these compounds can reduce the enzyme's activity by chelating the iron it requires. Similarly, 2,4-Pyridinedicarboxylic acid can inhibit metalloenzymes by chelating metal ions specific chemical inhibitors of ALKBH6 (AlkB homolog 6) have not been distinctly identified or characterized. ALKBH6 is part of the AlkB family of dioxygenases and is involved in processing methylated RNA and DNA lesions.