NSUN3 Inhibitors

NSUN3 inhibitors, as a chemical classification, primarily focus on the disruption of the enzyme's RNA methyltransferase activity, which is central to mitochondrial tRNA methylation. Given the specificity and importance of RNA methylation, particularly in mitochondrial function, targeting NSUN3 requires a nuanced approach to ensure that the desired inhibitory effect is achieved without inadvertently affecting other cellular processes. Most inhibitors in this category either directly or indirectly interfere with the RNA methylation process.

A significant fraction of the chemicals in this class, such as 5-Azacytidine, Decitabine, and RG108, are analogs of cytosine or adenosine that get incorporated into RNA or DNA. Their incorporation can alter the native structure or prevent methyl groups from being added, hence indirectly affecting NSUN3's function. Others, like Sinefungin, directly target the methyltransferase action by competing for the binding sites, effectively reducing the enzyme's ability to methylate its targets. Another strategy is the inhibition of associated pathways. For instance, 3-Deazaneplanocin A and its analog DZNEP disrupt methylation processes by affecting the S-adenosylhomocysteine hydrolase, a key component in methyl group transfers.