NSC 194308, a U2AF2-RNA complexes enhancer, increases association of the U2AF1-U2AF2-SF1-splice site RNA complex by binding a site between the U2AF2 RNA recognition motifs (RRM1 and RRM2). NSC 194308 inhibits pre-mRNA splicing by stalling spliceosome assembly at the point where U2AF helps recruit U2 snRNP to the branchpoint. NSC 194308 enhances the binding of pre-mRNA to U2AF2, selectively triggering cell death in leukemia cell lines containing spliceosome mutations.
References:
[1]. Rakesh Chatrikhi, et al. A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2-RNA complex. Cell Chem Biol. 2021 Aug 19;28(8):1145-1157.e6.
[2]. Riccardo Rozza, et al. Assessing the Binding Mode of a Splicing Modulator Stimulating Pre-mRNA Binding to the Plastic U2AF2 Splicing Factor. J Chem Inf Model. 2023 Dec 11;63(23):7508-7517.