Screening strategies for small molecules that inhibit SR protein-mediated splicing . (a) Compounds were screened for their ability to inhibit topoisomerase I phosphorylation of ASF/SF2, and then for repression of splicing of reporter constructs. (b) Compounds were screened for disruption of spliceosomal assembly, resulting in compounds that were indole derivatives. (c) Indole derivatives were screened for selective disruption of reporter pre-mRNAs where splicing was ASF/SF2 or SRp55 dependent. (d) Indole derivatives were screened for the ability to inhibit aberrant splicing. See text for further details.