CELF6 Inhibitors

Chemical inhibitors of CELF6 target various aspects of the protein's function, primarily focusing on its role in RNA binding and regulation of alternative splicing. Anisomycin acts by inhibiting peptidyl transferase activity on the ribosome, thereby disrupting the synthesis of newly formed CELF6 proteins. This inhibition can prevent CELF6 from interacting with RNA molecules and exerting its regulatory functions. Similarly, Isoginkgetin, a biflavonoid, and Meayamycin both target the splicing process. Isoginkgetin inhibits splicing factors, which can block the spliceosomal splicing necessary for CELF6 to regulate RNA processing. Meayamycin binds to the core spliceosome, which can inhibit the splicing regulatory activity of CELF6 by disrupting the splicing machinery it modulates.

Further along the splicing inhibition pathway, Pladienolide B, E7107, Madrasin, Sudemycin D6, Spliceostatin A, Herboxidiene, and Tetrocarcin A all act by inhibiting different components of the spliceosome. Pladienolide B and E7107 both bind to specific components of the spliceosome, which can disrupt its assembly or function, thereby preventing CELF6 from carrying out its regulatory role in splicing events. Madrasin selectively targets the SF3b complex and other components of the spliceosome, respectively, which can inhibit the splicing regulation activities that CELF6 is involved in. Spliceostatin A and Herboxidiene disrupt spliceosome assembly and splicing machinery interaction, which can prevent CELF6 from modulating alternative splicing events. Tetrocarcin A inhibits the spliceosome, thereby interfering with the regulation of splicing by CELF6. Additionally, Silvestrol inhibits eukaryotic initiation factor 4A (eIF4A), which can affect the translation of RNA targets regulated by CELF6, since eIF4A is essential for the translation of a subset of mRNAs. Lastly, Toyocamycin acts as an adenosine analog to inhibit RNA synthesis, which can reduce the availability of RNA molecules for CELF6 to bind and regulate, therefore inhibiting its function.