MS049 is a potent and selective inhibitor of PRMT4 (IC50 = 34 nM) and PRMT6 (IC50 = 43 nM). It is less active against additional type I PRMTs (IC50s = >130, >220, and 1.6 μM for PRMT1, PRMT3, and PRMT8, respectively) and displays no inhibition against type II or type III PRMTs nor any additional methyltransferases or nonepigenetic targets tested.

PRMT4:34 nM, PRMT6:43 nM

MS049 has been shown to reduce the H3R2me2a mark in HEK293 cells with an IC50 value of 0.97 μM and also, unexpectedly, to reduce H4R3me2a in HEK293 cells.

HEK293 cells were grown in 12-well plates in DMEM supplemented with 10% FBS, penicillin (100 units/mL) and streptomycin (100 μg/mL). 30% confluent cells were treated with different concentrations of compounds in triplicates or DMSO control for 72 h. Cells were lysed in 100 μL of total lysis buffer (20 mM Tris-HCl pH 8, 150 mM NaCl, 1 mM EDTA, 10 mM MgCl2, 0.5% TritonX-100, 12.5 U/mL benzonase, complete EDTA-free protease inhibitor cocktail ). After 3 min incubation at RT, SDS was added to final 1% concentration. Lysates were run on SDS-PAGE and immunoblotting was done as outlined below to determine Med12-Rme2a levels in Western blot. They are for reference only.