PUS10 Inhibitors

Chemical inhibitors of PUS10 can interfere with its activity in various ways, impacting the enzyme's ability to modify RNA. 6-Thioinosine, an analog of inosine, can be incorporated into RNA, where it may disrupt the pseudouridylation process essential for the proper function of transfer RNA, a direct target of PUS10. Tunicamycin, on the other hand, impedes N-linked glycosylation, a post-translational modification that could be crucial for PUS10's stability or localization within the cell, thereby indirectly affecting its function. Another compound, Roscovitine, targets cyclin-dependent kinases, which are key players in the regulation of transcription and RNA processing machinery. Although its action is not directly on PUS10, the inhibition of these kinases can result in reduced RNA modification activity by PUS10 due to alterations in the transcriptional landscape.

Actinomycin D and α-Amanitin are potent inhibitors of RNA polymerase I and II, respectively. Actinomycin D binds to DNA and prevents RNA synthesis, while α-Amanitin specifically targets RNA polymerase II, responsible for synthesizing messenger RNA. Both chemicals, by curtailing RNA synthesis, limit the availability of RNA substrates necessary for PUS10's activity. Compounds like Ricin and Cycloheximide disrupt protein synthesis, with Ricin depurinating rRNA and Cycloheximide inhibiting the translocation step during protein elongation. These disruptions can lead to an indirect inhibition of PUS10 by affecting cellular processes that support its function. Similarly, Puromycin causes premature termination of the growing polypeptide chain, thereby exerting an indirect effect on PUS10 by altering protein homeostasis in the cell. Triptolide and Mycophenolic Acid inhibit RNA polymerase II and inosine monophosphate dehydrogenase, respectively, leading to reduced RNA synthesis and availability for PUS10's modification processes. Lastly, Brefeldin A and Deferoxamine can indirectly inhibit PUS10 by altering protein trafficking and localization, and by chelating iron, which is a necessary cofactor for many enzymes, including potentially PUS10. These varied chemical inhibitors, by affecting RNA synthesis, protein synthesis, and enzyme cofactors, regulate the activity of PUS10 within the cell.