RBM22 Inhibitors

Chemical inhibitors of RBM22 target various aspects of the spliceosome machinery, where RBM22 is a critical component. Pladienolide B, Meayamycin, E7107, and Spliceostatin A all share a common mechanism of inhibiting the splicing activity of RBM22 by binding to the SF3b complex. This binding impedes the spliceosome's function, directly hindering RBM22's role in RNA splicing. Herboxidiene also targets the SF3b complex but may do so in a slightly different manner, still leading to the disruption of RBM22's activity in the spliceosome. These compounds ensure that the splicing process, which relies on the precise action of RBM22, is compromised, resulting in a functional inhibition of RBM22's role within this critical cellular process.

Further direct inhibition of RBM22 occurs through compounds like Madrasin and FR901464, which hinder the spliceosome assembly and splicing activity, thereby inhibiting the protein's function. Isoginkgetin, with its unique mechanism, prevents spliceosome assembly, thus impeding RBM22's ability to participate in RNA splicing. H3B-8800, although it selectively targets spliceosome mutations, can inhibit the activity of wild-type proteins like RBM22 that are part of the spliceosome. Plitidepsin (Aplidin) and Silvestrol exert their inhibitory effects by targeting factors associated with the splicing process, such as the eukaryotic translation elongation factor eEF1A2 and the DEAD-box RNA helicase eIF4A, respectively. By disrupting these related factors, the compounds indirectly but effectively reduce RBM22's functional activity in mRNA processing, leading to its inhibition.