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.

Product information

CAS Number: 134-47-4

Molecular Weight: 504.49

Formula: C21H16N2O9S2

Chemical Name: 4-hydroxy-7-{[(5-hydroxy-7-sulfonaphthalen-2-yl)carbamoyl]amino}naphthalene-2-sulfonic acid

Smiles: OS(=O)(=O)C1=CC(O)=C2C=CC(=CC2=C1)NC(=O)NC1=CC2=CC(=CC(O)=C2C=C1)S(O)(=O)=O

InChiKey: PCGISRHGYLRXSR-UHFFFAOYSA-N

InChi: InChI=1S/C21H16N2O9S2/c24-19-9-15(33(27,28)29)7-11-5-13(1-3-17(11)19)22-21(26)23-14-2-4-18-12(6-14)8-16(10-20(18)25)34(30,31)32/h1-10,24-25H,(H2,22,23,26)(H,27,28,29)(H,30,31,32)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 83.33 mg/mL (165.18 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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). AMI-1 free acid not only inhibits type I PRMTs (PRMT1, 3, 4 and 6) but also type II PRMT5. AMI-1 free acid specifically inhibits arginine, but not lysine, methyltransferase activity in vitro and does not compete for the AdoMet binding site. AMI-1 free acid inhibits methylation of GFP-Npl3 and cellular proteins. 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. AMI-1 free acid (1.2-2.4 mM; 48-72 hours) reduces S180 cell viability through the induction of cell apoptosis.

In Vivo:

AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) inhibits S180 viability in vivo. 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. AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) decreases the levels of H4R3me2s and H3R8me2s in a tumor xenograft model.

References:

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.

Products are for research use only. Not for human use.