METTL23 Inhibitors

Chemical inhibitors of METTL23 function by interacting with various biochemical pathways and molecular interactions that are essential for the activity of this protein. Sinefungin, for instance, competes with S-adenosylmethionine (SAM), the usual methyl donor substrate of METTL23, by binding to the SAM-binding site that METTL23 relies on for its methylation activity. This competitive inhibition effectively blocks the protein's ability to transfer methyl groups to its substrates. Similarly, Cycloleucine acts as a competitive inhibitor of methionine adenosyltransferase, an enzyme critical for the synthesis of SAM. With reduced availability of SAM, the enzymatic activity of METTL23 is hindered. 3-Deazaneplanocin A and Adenosine dialdehyde function through a related mechanism by inhibiting S-adenosylhomocysteine hydrolase, causing the accumulation of S-adenosylhomocysteine, a strong inhibitor of SAM-dependent methyltransferases, including METTL23. This leads to a functional blockade of METTL23's methylation capacity.

Further, BIX-01294, although primarily known for its inhibitory effects on histone methyltransferases, could alter histone methylation patterns in such a way that the chromatin context necessary for METTL23's proper function is disrupted. RG108 and Decitabine exert an indirect inhibitory effect by altering the DNA methylation landscape, which can influence the expression and function of proteins that are crucial for METTL23's regulatory mechanisms. Hydralazine and Epigallocatechin gallate work similarly by inhibiting DNA methyltransferase activity, leading to changes in gene expression patterns that could subsequently inhibit METTL23. On the other hand, 5'-Methylthioadenosine (MTA) directly competes with SAM, thereby inhibiting METTL23. Quercetin impedes protein kinases that are involved in phosphorylation cascades essential for METTL23's activity. Lastly, Chaetocin targets histone methyltransferases, potentially affecting the regulation of METTL23 through changes in the chromatin state. Each of these chemicals targets specific molecular interactions and pathways that are central to the functional activity of METTL23, thereby serving as effective inhibitors of its function.