Lamond Group Paper: “Identification of Small Molecule Inhibitors of Pre-mRNA Splicing” April 10, 2015 The Lamond Group in collaboration with Reinhard Lührmann, Max Planck Institute in Göttingen and the University of Dundee’s Drug Discovery Unit has published “Identification of Small Molecule Inhibitors of Pre-mRNA Splicing”, Pawellek, A. et al., (2014) JBC; PMID:25281741 / PMCID: PMC4263873. This study identified 10 new small molecules that both inhibit splicing in vitro and modify splicing of endogenous pre-mRNAs in human cell lines. These compounds were identified by screening a library of over 70,000 highly selected small molecules with drug like properties using a high throughput in vitro splicing assay. The group studied one of these small molecules, DDD00107587, which we termed “madrasin” i.e. 2-((7-methoxy-4-methylquinazolin-2-yl)amino)-5,6 dimethylpyrimidin-4(3H)-one RNA splicing inhibitor, in more detail. Madrasin modulates splicing of multiple pre-mRNAs in cells, promotes a specific reorganisation of subnuclear protein localisation and stalls spliceosome assembly at the A complex.
