A novel arginine methyltransferase inhibitor with cellular activity

Via virtual screening we identified a thioglycolic amide as an arginine methyltransferase (PRMT) inhibitor and tested it and related compounds against the fungal PRMT RmtA and human PRMT1. Compound RM65 was the most potent druglike inhibitor (IC50-PRMT1: 55.4 μM) and showed histone hypomethylation in HepG2 cells. Docking studies proposed binding at the substrate and SAM cofactor binding pocket. It may serve as a lead for further PRMT inhibitors useful for the treatment for hormone dependent cancers.

A new cell permeable arginine methyltransferase inhibitor by fragment based virtual screening is reported.Figure optionsDownload as PowerPoint slide