SF3B3 Inhibitors

SF3B3 inhibitors are a class of compounds that interact with the SF3B3 protein or its associated complexes and pathways to modulate pre-mRNA splicing. The SF3B3 protein is a subunit of the SF3B complex, which is essential for the recognition and proper removal of introns from pre-mRNA transcripts. This splicing process is critical for generating mature and translatable mRNA molecules. Chemical compounds that target SF3B3 or the SF3B complex can alter the normal splicing pattern, resulting in defective mRNA and subsequent changes in protein synthesis.

Many of the identified inhibitors, such as pladienolide B and its derivatives, interact directly with the SF3B complex, although their precise binding to the SF3B3 subunit may not be fully characterized. These compounds, including E7107 and spliceostatin A, bind to the complex and disrupt its function, which can lead to the inhibition of the splicing process and the production of aberrant mRNA transcripts. This disruption can have cascading effects on cell function due to the production of dysfunctional or non-functional proteins. Other compounds, like isoginkgetin, indirectly affect the splicing machinery by inhibiting the assembly of the spliceosome, of which the SF3B complex is a critical component. By interrupting the formation of a fully functional spliceosome, these inhibitors can cause a general downregulation of splicing activity