MS023 is a potent, selective, and cell-active inhibitor of human type I PRMTs with IC50 of 4-119 nM.
MS023 potently inhibits PRMT1 (IC50 = 30 9 nM), PRMT3 (IC50 = 119 14 nM), PRMT4 (IC50 = 83 10 nM), PRMT6 (IC50 = 4 0.5 nM), and PRMT8 (IC50 = 5 0.1 nM). Importantly, MS023 does not inhibit any type II PRMTs (PRMT5 and 9) and type III PRMT (PRMT7) at concentrations up to 10 M. MS023 displays high potency for type I PRMTs including PRMT1, -3, -4, -6, and -8 but is completely inactive against type II and type III PRMTs, protein lysine methyltransferases and DNA methyltransferases. MS023 potently decreases cellular levels of histone arginine asymmetric dimethylation. It also reduces global levels of arginine asymmetric dimethylation and concurrently increased levels of arginine monomethylation and symmetric dimethylation in cells.