MS023 is a potent, selective, and cell-active Type I PRMT inhibitor with IC50 values of 30 nM, 119 nM, 83 nM, 4 nM, and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively.

PRMT1:30 nM, PRMT8:5 nM, PRMT4:83 nM, PRMT3:119 nM, PRMT6:4 nM

MS023 potently reduces cellular levels of H4R3me2a in MCF7 and HEK293 cells by inhibiting PRMT1/6 methyltransferase activity with IC50 of 9 nM and 56 nM, respectively. MS023 also inhibits cell growth and potentially induces growth arrest and flattening morphology at low concentrations. [1]

PRMT Biochemical Assays: A scintillation proximity assay (SPA) is used for assessing the effect of test compounds on inhibiting the methyl transfer reaction catalyzed by PRMTs. In brief, the tritiated S-adenosyl-L-methionine (3H-SAM) is used as the donor of methyl group. The (3H) methylated biotin labeled peptide is captured in a streptavidin/scintillant-coated microplate, which brings the incorporated 3H-methyl and the scintillant to close proximity resulting in light emission that is quantified by tracing the radioactivity signal (counts per minute) as measured by a TopCount NXT Microplate Scintillation and Luminescence Counter. When necessary, nontritiated SAM is used to supplement the reactions. The IC50 values are determined under balanced conditions at Km concentrations of both substrate and cofactor by titration of test compounds in the reaction mixture.