METTL11A Inhibitors

Chemical inhibitors of METTL11A encompass a range of compounds that interfere with its enzymatic function through various biochemical mechanisms. S-Adenosylhomocysteine (SAH), a product of METTL11A's reaction, can inhibit the enzyme by competing with S-adenosylmethionine (SAM), the methyl donor, effectively blocking the active site and reducing the enzyme's methylation activity. Similarly, Methylthioadenosine (MTA), a byproduct of polyamine synthesis, competes with SAM, thus diminishing METTL11A activity. Periodate-oxidized adenosine also inhibits METTL11A by binding to the SAM binding site, thereby preventing the necessary interaction of SAM with METTL11A for its function. Other compounds that inhibit METTL11A do so by altering the availability of SAM or SAH. Sinomenine and hydralazine can influence the SAM to SAH ratio within the cell, thereby indirectly diminishing METTL11A activity. Compounds such as 3-Deazaneplanocin A, Neplanocin A, Adenosine dialdehyde, and Cycloleucine act upstream by inhibiting S-adenosylhomocysteine hydrolase or S-adenosylmethionine synthetase, leading to an increase in SAH or a decrease in SAM, respectively, which in turn affects METTL11A activity. Decitabine incorporates into DNA and affects DNA methyltransferases, which can lead to a reduced availability of SAM, indirectly impeding METTL11A's function. Additionally, RG108 and BIX-01294, by targeting DNA and H3K9 methyltransferases, respectively, can alter the intracellular levels of SAM, which can decrease METTL11A activity due to limited substrate availability. These diverse chemical inhibitors, through their unique mechanisms of action, all converge on the common outcome of inhibiting the enzymatic activity of METTL11A.