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MSD in collaboration with the SGC has developed a dual activity chemical probe MRK-990 for PRMT9 and PRMT5. When used in parallel with selective chemical probes for PRMT5 (e.g., GSK591 and LLY-283), MRK-990 can be used to study the biological role of PRMT9.
MRK-990 inhibits PRMT9 with IC50 = 10 nM and PRMT5 with IC50 = 30 nM in a radioactivity based methyltranserase assay. In an in-cell western assay, MRK-990 inhibits the methylation of SAP145 (PRMT9) with IC50 = 145 nM, and dimethylarginine (PRMT5) with IC50 = 519 nM. MRK-990-NC is a closely related negative control with IC50 > 10 micromolar.