A630018P17Rik Inhibitors

Chemical inhibitors of Transcription Elongation Factor A (SII) N-terminal and central domain containing can affect the transcription process through various mechanisms. DRB targets this protein by blocking the phosphorylation of RNA polymerase II's C-terminal domain (CTD), a crucial step in the elongation phase of transcription. Similarly, Flavopiridol acts upstream by inhibiting cyclin-dependent kinases (CDKs) that are necessary for the CTD phosphorylation, which in turn is essential for the functionality of Transcription Elongation Factor A (SII). On a more direct level, α-Amanitin binds to RNA polymerase II, impeding its ability to move along the DNA and thus stifling the elongation process. Triptolide exerts its inhibitory effect by covalently modifying subunits of RNA polymerase II, effectively shutting down the transcription machinery.

Further down the transcription pathway, Actinomycin D intercalates into DNA, obstructing RNA polymerase II from advancing and halting the elongation process. Cordycepin, by incorporating itself into the RNA chain, leads to premature termination of mRNA synthesis, thereby inhibiting the role of Transcription Elongation Factor A (SII). Inhibition can also occur indirectly through the intervention in the transcription-associated processes, as seen with ICRF-187 which chelates iron, a vital cofactor for ribonucleotide reductase, indirectly affecting transcription. Topoisomerase inhibitors like Camptothecin and Etoposide prevent the relaxation of DNA supercoils, necessary for transcription elongation, therefore indirectly affecting the function of Transcription Elongation Factor A (SII). Other compounds such as Rocaglamide, Betulinic Acid, and Silvestrol disrupt different aspects of the transcription and translation machinery, which can indirectly inhibit the function of Transcription Elongation Factor A (SII), either by affecting the initiation and elongation phases of transcription or by inducing the degradation of RNA polymerase II.