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.