screen-shot-2015-04-10-at-11-30-41The 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.