METTL8 Inhibitors

Chemical inhibitors of METTL8 employ different mechanisms to deter its function. 3-Deazadenosine can lead to the accumulation of S-adenosylhomocysteine, which acts as a potent inhibitor of METTL8 by binding to its active site and obstructing the methyltransfer reaction. Meclofenamic acid competes directly with the methyl donors that METTL8 requires, effectively inhibiting its enzymatic activity. This competitive inhibition ensures that the methyl groups necessary for METTL8's function are not transferred to its substrates. 5'-Methylthioadenosine mimics the natural substrates of METTL8, occupying its active site and preventing the enzyme from catalyzing the methylation of its intended targets. Sinomenine can alter the conformation of METTL8, which is essential for the proper binding of substrates or co-factors, thereby disrupting its function. Decitabine is another inhibitor that, although primarily targeting DNA methyltransferases, depletes the available methyl donor pool, which can lead to an indirect inhibition of METTL8's activity. Further into the spectrum of chemical inhibitors, RG108, despite its principal role in inhibiting DNA methyltransferases, can reduce the availability of methyl groups necessary for METTL8 function. BIX-01294's inhibition of G9a methyltransferase can influence the global methylation patterns within the cell, which may have downstream effects on METTL8 activity. Chaetocin's ability to inhibit SUV39H1 affects histone methylation states and could indirectly interfere with METTL8's methylation activity. EPZ004777 directly targets DOT1L, altering histone methylation landscapes that can impact METTL8. Quercetin obstructs various kinases, and the resulting changes in phosphorylation states can interfere with METTL8 regulatory mechanisms. Sinefungin offers a broader approach, acting as a universal methyltransferase inhibitor and competing with S-adenosylmethionine, thus preventing METTL8 from transferring methyl groups. Lastly, Disulfiram, through its inhibition of dopamine beta-hydroxylase, can modulate catecholamine levels, which in turn can influence regulatory pathways that govern METTL8's activity. Each of these inhibitors disrupts METTL8's function through a strategic blockade or alteration of its critical operational pathways.