Fibrillarin-like 1 Inhibitors

Chemical inhibitors of Fibrillarin-like 1 can be classified based on their mechanism of action and how they interact with the protein's functional domains or associated biochemical pathways. S-Adenosyl homocysteine competes with S-adenosylmethionine, the natural methyl donor substrate of Fibrillarin-like 1, thus directly inhibiting its methyltransferase activity. This competitive inhibition is a common approach to reduce the functional activity of enzymes by providing an alternative substrate that binds to the active site without being transformed into a product, leading to a decrease in the enzyme's catalytic activity. Similarly, Methylthioadenosine can occupy the active site of Fibrillarin-like 1, resembling the structure of S-adenosylmethionine closely enough to prevent the enzyme from catalyzing its normal methylation reactions. BIX-01294, though primarily targeting a different methyltransferase, can also inhibit Fibrillarin-like 1 by competing with the enzyme's substrate binding, resulting in a decrease in its methyltransferase function.

The inhibition of Fibrillarin-like 1 extends to chemicals that interfere with the methylation status of nucleic acids, which are critical for the protein's role in processing and modifying rRNA. Compounds such as 5-Azacytidine and Decitabine incorporate into RNA, disrupting the methylation process at sites where Fibrillarin-like 1 would typically act. This incorporation acts as a roadblock for the enzyme, reducing its ability to interact with its RNA substrates. Zebularine, by inhibiting DNA methyltransferases, might change the methylation pattern of DNA in a way that it influences the RNA substrates of Fibrillarin-like 1, thus indirectly inhibiting its activity. Quercetin inhibits protein kinases that are involved in the phosphorylation of proteins that can regulate Fibrillarin-like 1, thereby reducing its activity by preventing activation through these kinases. Another compound, Chaetocin, is a known inhibitor of histone methyltransferases and could reduce the methylation capacity of Fibrillarin-like 1 by competing with the enzyme's substrates. Disulfiram and Hydralazine inhibit metalloenzymes and DNA methyltransferases, respectively, and can reduce the activity of Fibrillarin-like 1 by changing the metal cofactor availability or the methylation patterns of nucleic acids that Fibrillarin-like 1 interacts with. Finally, Epigallocatechin gallate, a DNA methyltransferase inhibitor, can also result in the inhibition of Fibrillarin-like 1 activity by altering the methylation patterns of its nucleic acid substrates.