AMI-1 free acid

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[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

IC50: 8.8 μM (PRMT1), 3.0 μM (yeast-Hmt1p)[1]

AMI-1 free acid can inhibit the in vitro methylation reactions performed by all five recombinantly active PRMTs (PRMT1, -3, -4, and -6 and Hmt1p)[2]. AMI-1 free acid not only inhibits type I PRMTs (PRMT1, 3, 4 and 6) but also type II PRMT5[2]. AMI-1 free acid specifically inhibits arginine, but not lysine, methyltransferase activity in vitro and does not compete for the AdoMet binding site[3]. AMI-1 free acid inhibits methylation of GFP-Npl3 and cellular proteins[3]. AMI-1 free acid (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[4]. AMI-1 free acid (1.2-2.4 mM; 48-72 hours) reduces S180 cell viability through the induction of cell apoptosis[4]. Cell Viability Assay[4] Cell Line: S180 cells, U2OS cells Concentration: 0.6 mM, 1.2 mM, 2.4 mM Incubation Time: 48 hours, 72 hours, 96 hours Result: Inhibited the cell viability. Apoptosis Analysis[4] Cell Line: S180 cells Concentration: 1.2 mM, 2.4 mM Incubation Time: 48 hours, 72 hours Result: Increased the percentages of cells undergoing apoptosis.

AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) inhibits S180 viability in vivo[4]. AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) downregulates PRMT5 but does not regulate the expression of PRMT7 in a tumor xenograft model[4]. AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) decreases the levels of H4R3me2s and H3R8me2s in a tumor xenograft model[4]. Animal Model: 6-7 weeks old male Kunming mice (18-22 g), with S180 cells xenograft[4] Dosage: 0.5 mg Administration: Intratumorally, daily, for 7 days Result: Decreased tumor weight.

[1]. Donghang Cheng, et al. Small Molecule Regulators of Protein Arginine Methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9.

[2]. Zhang, B., et al. Targeting protein arginine methyltransferase 5 inhibits colorectal cancer growth by decreasing arginine methylation of eIF4E and FGFR3. Oncotarget. 2015 Sep 8;6(26):22799-811.

[3]. Donghang Cheng, et al. Small Molecule Regulators of Protein Arginine Methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9.

[4]. Baolai Zhang, et al. Arginine Methyltransferase inhibitor-1 Inhibits Sarcoma Viability in vitro and in vivo. Oncol Lett. 2018 Aug;16(2):2161-2166.