ZRSR1 Inhibitors

Chemical inhibitors of ZRSR1 function by targeting the splicing machinery of which ZRSR1 is an integral component. Pladienolide B and Meayamycin engage directly with the SF3b complex within the spliceosome, which is pivotal for the splicing of pre-mRNA. The binding of these molecules disrupts the normal functioning of the spliceosome, leading to the inhibition of ZRSR1, as it cannot perform its role in the splicing process when the SF3b complex is compromised. Similarly, E7107 and Spliceostatin A exert their inhibitory effects by interacting with the spliceosome. E7107's influence on the SF3b complex impedes the proper assembly and function of the splicing machinery, while Spliceostatin A's binding to the spliceosome constrains the splicing activity, thereby inhibiting ZRSR1. Furthermore, compounds like Thailanstatin A, Herboxidiene, Madrasin, and Isoginkgetin also impair the spliceosome's function, leading to a consequent inhibition of ZRSR1. These chemicals bind variously to the SF3b complex or to other components of the spliceosome, disrupting the essential splicing mechanisms in which ZRSR1 is involved.

Other chemicals exert an indirect effect on ZRSR1 by targeting related pathways or machinery. Plitidepsin interacts with eEF1A2, a factor involved in the protein synthesis pathway, and this interaction can influence the splicing process that involves ZRSR1, leading to its functional inhibition. Silvestrol, although primarily known to inhibit translation initiation, can indirectly affect the splicing process. By inhibiting translation initiation, Silvestrol may reduce the levels of proteins that are necessary for the proper function of the spliceosome, and consequently ZRSR1's activity in mRNA splicing is hindered. These varied modes of action by different chemical inhibitors result in the functional inhibition of ZRSR1 by disrupting the splicing process or the cellular components that are necessary for its activity.