CMP-5 hydrochloride is a potent and selective PRMT5 inhibitor, while displays no activity against PRMT1/4/7 enzymes. It selectively blocks S2Me-H4R3 by inhibiting PRMT5 methyltransferase activity on histone preparations.

MTH2 (cells):9.2 μM , MTH1 (cells):3.7 μM , Th2 cells (human):36.1 μM , Th1 cells (human):26.9 μM

CMP-5 (0-100 μM; 24-72 hours) exhibits selective toxicity towards lymphoma cells, while showing limited toxicity to normal resting B lymphocytes, even with extended incubation. CMP-5 (0-40 μM; 24 hours) preferentially inhibits the proliferation of human Th1 cells over Th2 cells (43% vs. 9% inhibition, respectively), with IC50 values of 26.9 μM for Th1 cells and 31.6 μM for Th2 cells, indicating differential sensitivity to PRMT5 inhibition. CMP-5 (40 μM; 24 hours) reduces p-BTK and pY(416)SRC expression in 60A cells compared to the DMSO-treated group. Additionally, CMP-5 (25 μM; 24 hours) alone inhibits mouse Th1 cell proliferation by 91%; however, the addition of varying doses of IL-2 enhances proliferation, peaking at 5 ng/ml [1].