Urea J Acid (AMI-1; AMI 1) is a selective inhibitor of Histone Methyltransferase (HMT) with anti-inflammatory activity. It inhibits HMT with an IC50 of 3.0 μM and 8.8 μM for yeast Hmt1p and human PRMT1, respectively.
Physicochemical Properties
| Molecular Formula | C21H16N2O9S2 |
| Molecular Weight | 504.4897 |
| Exact Mass | 504.03 |
| CAS # | 134-47-4 |
| Related CAS # | AMI-1;20324-87-2 |
| PubChem CID | 67254 |
| Appearance | Light brown to brown solid powder |
| Density | 1.798 g/cm3 |
| Melting Point | 86-88 °C |
| Index of Refraction | -45 ° (C=1, AcOH) |
| LogP | 5.849 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 34 |
| Complexity | 886 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PCGISRHGYLRXSR-UHFFFAOYSA-N |
| InChi Code | 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) |
| Chemical Name | 4-hydroxy-7-[(5-hydroxy-7-sulfonaphthalen-2-yl)carbamoylamino]naphthalene-2-sulfonic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | AMI-1 free acid has been shown to inhibit the in vitro methylation processes of all five recombinantly active PRMTs (PRMT1, -3, -4, and -6, as well as Hmt1p)[2]. AMI-1 free acid inhibits both type I PRMTs (PRMT1, 3, 4, and 6) and type II PRMT5 [2]. In vitro, AMI-1 free acid inhibits arginine methyltransferase activity but not lysine, and it does not compete with AdoMet for the binding site[3]. Free acid prevents the methylation of GFP-Npl3 and cellular proteins[3]. AMI-1 free acid (0.6-2.4 mM; 48-96 hours) reduces sarcoma cell survival in S180 and U2OS cells in a time- and dose-dependent manner in vitro[4]. AMI-1 free acid (1.2-2.4 mM; 48-72 hours) lowers S180 cell viability by inducing cell death [4]. |
| ln Vivo | S180 viability is inhibited in vivo by AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days)[4]. In a tumor xenograft model, AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) downregulates PRMT5 but does not control PRMT7 expression[4]. In a tumor xenograft model, AMI-1 free acid (0.5 mg; intratumorally; daily; for 7 days) reduces the levels of H4R3me2s and H3R8me2s[4]. |
| Cell Assay |
Cell Viability Assay[4] Cell Types: S180 cells, U2OS cells Tested Concentrations: 0.6mM, 1.2mM, 2.4mM Incubation Duration: 48 hrs (hours), 72 hrs (hours), 96 hrs (hours) Experimental Results: Inhibited the cell viability. Apoptosis Analysis[4] Cell Types: S180 cells Tested Concentrations: 1.2mM, 2.4mM Incubation Duration: 48 hrs (hours), 72 hrs (hours) Experimental Results: Increased the percentages of cells undergoing apoptosis. |
| Animal Protocol |
Animal/Disease Models: 6- 7 weeks old male Kunming mice (18-22 g), with S180 cells xenograft[4] Doses: 0.5 mg Route of Administration: Intratumorally, daily, for 7 days Experimental Results: diminished tumor weight. |
| References |
[1]. 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. [2]. Arginine Methyltransferase inhibitor-1 Inhibits Sarcoma Viability in vitro and in vivo. Oncol Lett. 2018 Aug;16(2):2161-2166. [3]. Small Molecule Regulators of Protein Arginine Methyltransferases. J Biol Chem. 2004 Jun 4;279(23):23892-9. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~83.33 mg/mL (~165.18 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9822 mL | 9.9110 mL | 19.8220 mL | |
| 5 mM | 0.3964 mL | 1.9822 mL | 3.9644 mL | |
| 10 mM | 0.1982 mL | 0.9911 mL | 1.9822 mL |