Pol I/II/III RPB8 Inhibitors

The chemical class known as Pol I/II/III RPB8 Inhibitors encompasses a range of compounds that can indirectly inhibit the function of the RPB8 subunit of RNA polymerases I, II, and III by various mechanisms. These inhibitors are not directly associated with the RPB8 protein but can interfere with broader transcriptional processes or with specific stages of RNA synthesis in which RPB8 plays a role.

The first group includes compounds that bind directly to RNA polymerases, such as α-Amanitin, which targets RNA polymerase II and by extension affects the RPB8 subunit. Similarly, Actinomycin D and DRB interfere with the transcription process by preventing RNA polymerase binding to DNA or by blocking the transition from transcription initiation to elongation, respectively. Other compounds, like Triptolide, target other subunits of RNA polymerase II, causing an indirect effect on RPB8. The second group includes compounds like Cordycepin and Cytosine arabinoside, which are nucleoside analogs that incorporate into RNA or DNA, leading to the inhibition of RNA chain elongation or reduction of DNA templates available for transcription. Compounds like Tunicamycin impact post-translational modifications of proteins, which can affect the proper assembly and function of the RNA polymerase complexes. Flavopiridol and ICRF-193 target other cellular enzymes such as CDKs and topoisomerase II, which are necessary for proper transcriptional regulation and indirectly impact the function of RPB8. CX-5461, although specific for RNA polymerase I, also has an indirect effect on RPB8 by inhibiting the transcription initiation complex of Pol I.