SFRS8 Inhibitors

Chemical inhibitors of SFRS8 primarily function by targeting the spliceosome, a complex molecular machine responsible for the removal of introns from pre-mRNA in the splicing process. Pladienolide, and its derivative E7107, bind to the SF3b complex, a key component of the spliceosome, and by doing so, they impair the recognition of branch point sequences. This action inhibits the splicing activity where SFRS8 is involved, affecting the regulation of gene expression at the RNA level. Meayamycin, with its similar mode of action, binds to the same complex, disrupting the interaction with branch point adenosine, which is crucial during the splicing process. This inhibition directly affects SFRS8's ability to facilitate the assembly of the spliceosome. FR901464 also interacts with the SF3b complex, inhibiting the normal function of spliceosome components, including SFRS8, by preventing proper splice site recognition.

Further contributing to the range of inhibitors, Spliceostatin A and Herboxidiene (also known as GEX1A) target the SF3b complex, of which SFRS8 is a part. By inhibiting the complex's function, these chemicals interfere with SFRS8's role in spliceosome assembly and function. Thailanstatin A and Madrasin follow a similar inhibition pathway by binding to the SF3b complex, leading to a disruption in the recognition and binding of splicing sites, which is essential for the splicing process and, consequently, SFRS8's activity. Isoginkgetin, a biflavonoid, inhibits the assembly of the spliceosome, thus indirectly inhibiting SFRS8's role in the splicing process. Plitidepsin binds to eEF1A2, a protein involved in translation, and by doing so, it indirectly affects SFRS8 since the spliceosome assembly depends on proper protein synthesis. Any alteration in translation can influence the availability and functionality of splicing factors, including SFRS8.