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EPZ015666 is a potent, selective, competitive PRMT5 inhibitor (IC50 = 22 nM). EPZ015666 exhibits >10,000-fold specificity for PRMT5 vs. other methyltransferases. EPZ015666 blocks the association of PRMT5 with methylosome protein 50 (WDR77), which is necessary to form an active methyltransferase complex. Treatment of MCL cell lines with nM concentrations of EPZ015666 leads to inhibition of SmD3 methylation and cell death."