ms023

Description: MS023 is a novel potent, selective, and cell-active inhibitor of human type I PRMTs (Protein arginine methyltransferases) with IC50 ranging from 4 to 119 nM. PRMTs play a crucial role in a variety of biological processes. Overexpression of PRMTs has been implicated in various human diseases including cancer. MS023 displayed high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but was completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. A crystal structure of PRMT6 in complex with MS023 revealed that MS023 binds the substrate binding site. MS023 potently decreased cellular levels of histone arginine asymmetric dimethylation. It also reduced global levels of arginine asymmetric dimethylation and concurrently increased levels of arginine monomethylation and symmetric dimethylation in cells. We also developed MS094, a close analog of MS023, which was inactive in biochemical and cellular assays, as a negative control for chemical biology studies.

References: ACS Chem Biol. 2016 Mar 18; 11(3):772-781.