IC50: 8.8 μM (PRMT1), 3.0 μM (yeast-Hmt1p)
AMI-1 can inhibit the in vitro methylation reactions performed by all five recombinantly active PRMTs (PRMT1, -3, -4, and -6 and Hmt1p). AMI-1 not only inhibits type I PRMTs (PRMT1, 3, 4 and 6) but also type II PRMT5. AMI-1 specifically inhibits arginine, but not lysine, methyltransferase activity in vitro and does not compete for the AdoMet binding site. AMI-1 inhibits methylation of GFP-Npl3 and cellular proteins. AMI-1 (0.6-2.4 mM; 48-96 hours) inhibits the cell viability of sarcoma in S180 and U2OS cells in a time-dependent and dose-dependent manner in vitro. AMI-1 (1.2-2.4 mM; 48-72 hours) reduces S180 cell viability through the induction of cell apoptosis.
Cell Viability Assay
Apoptosis Analysis
AMI-1 (0.5 mg; intratumorally; daily; for 7 days) inhibits S180 viability in vivo. AMI-1 (0.5 mg; intratumorally; daily; for 7 days) downregulates PRMT5 but does not regulate the expression of PRMT7 in a tumor xenograft model. AMI-1 (0.5 mg; intratumorally; daily; for 7 days) decreases the levels of H4R3me2s and H3R8me2s in a tumor xenograft model.