AMI-1 free acid is a potent, cell-permeable and reversible inhibitor of protein arginine N-methyltransferases (PRMTs), with IC50s of 8.8 μM and 3.0 μM for human PRMT1 and yeast-Hmt1p, respectively. AMI-1 free acid exerts PRMTs inhibitory effects by blocking peptide-substrate binding.
The protein arginine N-methyltransferases (PRMTs) are a group of enzymes that monomethylate or dimethylate the arginine side chains. AMI-1 free acid is a potent and cell-permeable PRMT inhibitor with IC50 values of 8.81μM and 3.03μM for PRMT1 and Hmt1p, respectively. It is also a selective HIV-1 reverse transcriptase inhibitor. AMI-1 at a concentration of 2 - 10μM inhibited Npl3 methylation in Hela cells. AMI-1 also inhibited arginine methylation of the endogenously methylated protein, Sam68[5]. AMI-1 inhibited the viability of S180 and U2OS cells with IC50 values of 0.31 ± 0.01mM and 0.75 ± 0.02mM, respectively. In mice inoculated with S180 cells, treatment with 0.5mg AMI-1 for 7 days significantly decreased tumor weight compared to the vehicle-treated controls. AMI-1 treatment also significantly downregulated the expression of PRMT5 and decreased the levels of H4R3me2s and H3R8me2s in mice implanted with S180 cells[6].
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