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Amonafide (formerly NSC308847, AS1413; AS-1413; NSC-308847; Amonafide; Nafidimide; Benzisoquinolinedione; Quinamed; Xanafide), an imide derivative of naphthalic acid, is an inhibitor of topoisomerase II (Topo II) and also a DNA intercalator being investigated for the treatment of cancer.
Physicochemical Properties
| Molecular Formula | C16H17N3O2 |
| Molecular Weight | 283.33 |
| Exact Mass | 283.132 |
| Elemental Analysis | C, 67.83; H, 6.05; N, 14.83; O, 11.29 |
| CAS # | 69408-81-7 |
| Related CAS # | :69408-81-7 150091-68-2 (2HCl)618863-54-0 (L-malate) 618863-60-8 |
| PubChem CID | 50515 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 500.2±35.0 °C at 760 mmHg |
| Melting Point | 162-164ºC |
| Flash Point | 256.3±25.9 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.681 |
| LogP | 0.06 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 21 |
| Complexity | 437 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1N(C(C2=CC(N)=CC3=CC=CC1=C23)=O)CCN(C)C |
| InChi Key | UPALIKSFLSVKIS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H17N3O2/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21/h3-5,8-9H,6-7,17H2,1-2H3 |
| Chemical Name | 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione |
| Synonyms | AS1413; NSC308847; AS1413; NSC-308847; AS-1413; NSC 308847; AS 1413; Amonafide; Nafidimide; Benzisoquinolinedione; Quinamed; Xanafide |
| HS Tariff Code | 2934.99.03.00 |
| 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
| Targets | Topoisomerase II | ||
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| ln Vivo |
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| Cell Assay | In studies that track survival after one-hour drug treatments, 2 × 106 cells are resuspended in 2 mL of warm (37°C) HBSS with 5% PCS; adding less than 50 μL of the appropriate drug (amonafide) brings the cell count down to the desired level. Ten milliliters of ice-cold PBS are added to the cells after they have been incubated for sixty minutes at 37°C. Next, the cells are centrifuged for 10 minutes at 4°C at 200 × g. To determine the number of surviving clonogenic cells, the cells are washed again, resuspended in HBSS containing 5% PCS, and added to the agar-medium mixture[2]. | ||
| Animal Protocol |
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| Toxicity/Toxicokinetics |
Toxicity Data Mouse(iv): LD50: 69 mg/kg |
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| References |
[1]. Amonafide: a potential role in treating acute myeloid leukemia. Expert Opin Investig Drugs. 2011 Jul;20(7):995-1003. [2]. In vitro toxicity and DNA cleaving capacity of benzisoquinolinedione (nafidimide; NSC 308847) in human leukemia. Cancer Res. 1987 Feb 15;47(4):1040-4. [3]. In vitro activity of amonafide against primary human tumors compared with the activity of standard agents. Invest New Drugs. 1988 Jun;6(2):79-85. |
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| Additional Infomation |
5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione is a member of isoquinolines. Amonafide is a substance that is being studied in the treatment of cancer. It belongs to the families of drugs called topoisomerase inhibitors and intercalating agents. Amonafide Dihydrochloride is the dihydrochloride salt of amonafide, an imide derivative of naphthalic acid. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in protein-associated strand breaks and impaired DNA and RNA synthesis. Amonafide is an imide derivative of naphthalic acid. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in protein-associated strand breaks and impaired DNA and RNA synthesis. Drug Indication Investigated for use/treatment in breast cancer, ovarian cancer, and prostate cancer. Mechanism of Action Amonafide is a DNA intercalating agent and inhibitor of topoisomerase II that has been extensively studied in patients with malignant solid tumors. Amonafide has also been studied in patients with AML. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.82 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 25.0 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 (7.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5295 mL | 17.6473 mL | 35.2945 mL | |
| 5 mM | 0.7059 mL | 3.5295 mL | 7.0589 mL | |
| 10 mM | 0.3529 mL | 1.7647 mL | 3.5295 mL |