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Catalog No.S1367 Synonyms: NSC308847,AS1413

6 publications

Amonafide Chemical Structure

CAS No. 69408-81-7

Amonafide (NSC308847, AS1413) produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.

Selleck's Amonafide has been cited by 6 publications

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Description Amonafide (NSC308847, AS1413) produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.
Topo II [1]
In vitro

Through a topoisomerase II-mediated reaction, Amonafide treatment produces DNA single-strand breaks (SSB), double-strand breaks (DSB), and DNA-protein cross-links in human myeloid leukemia cells. Amonafide treatment inhibits conlony formation of the leukemic cell lines and the normal human bone marrow GM-CFC in a dose-dependent manner. Amonafide does not produce topoisomerase I-mediated DNA cleavage even at 100 μM. The m-AMSA-resistant line is less than 2-fold resistant to Amonafide [1] Amonafide interferes with the DNA breakage-reunion activity of mammalian DNA topoisomerase II resulting in DNA cleavage stimulation. [2] Compared with those of other antitumor drugs, Amonafide-stimulated cleavage intensity patterns are markedly different. Amonafide highly prefers a cytosine, and excludes guanines and thymines instead, at position -1, with lower preference for an adenine at position +1. [3] Topoisomerase II-mediated DNA cleavage induced by Amonafide is affected only slightly (less than 3-fold) by 1 mM ATP, suggeting that Amonafide is an ATP-insensitive topoisomerase II inhibitor in contrast to doxorubicin, etoposide, and mitoxantrone. [4] Amonafide significantly inhibits the growth of HT-29, HeLa, and PC3 cells with IC50 of 4.67 μM, 2.73 μM, and 6.38 μM, respectively. [5] Amonafide is unaffected by P-glycoprotein-mediated efflux, unlike those of the classical topoisomerase II inhibitors (daunorubicin, doxorubicin, idarubicin, etoposide, and mitoxantrone). [6]


Cell Research:[5]
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  • Cell lines: HT-29, HeLa, and PC3
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 72 hours
  • Method: All cell lines are in the logarithmic phase of growth when the assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) is carried out. Cells are harvested and seeded into 96-well tissue culture plates at a density of 2.5 × 103 cells/well in 150 μL aliquots of medium. The concentrations tested are serial dilutions of a stock solution (10 μM in DMSO) with phosphate-buffered saline (PBS) and are added 24 hours later. The assay is ended after 72 hours of Amonafide exposure and PBS is used as a negative control. After 72 hours treatment, cells are washed twice with PBS, and then 50 μL/well of MTT reagent (1 mg/mL in PBS) together with 150 μL/well of prewarmed medium are added. The plates are returned to the incubator for 4 hours. Subsequently, DMSO is added as solvent. Absorbance is determined at 570 nm with a Microplate reader. All experiments are performed at least three times, and the average of the percentage absorbance is plotted against concentration. Then, the concentration of Amonafide required to inhibit 50% of cell growth (IC50) is calculated for Amonafide.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 57 mg/mL (201.17 mM)
Ethanol 4 mg/mL (14.11 mM)
Water Insoluble

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Chemical Information

Molecular Weight 283.33


CAS No. 69408-81-7
Storage powder
in solvent
Synonyms NSC308847,AS1413
Smiles CN(C)CCN1C(=O)C2=CC=CC3=CC(=CC(=C32)C1=O)N

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01066494 Unknown status Drug: Amonafide + cytarabine Acute Myeloid Leukemia Antisoma Research January 2010 Phase 2
NCT00273884 Completed Drug: Amonafide L-Malate|Drug: Cytarabine Acute Myeloid Leukemia Xanthus Pharmaceuticals Inc. August 2005 Phase 2
NCT00087854 Completed Drug: Amonafide L-malate (drug) Prostate Cancer Xanthus Pharmaceuticals Inc. March 2004 Phase 1|Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID