Home DNA Damage/DNA Repair Topoisomerase inhibitor Amonafide For research use only.

Amonafide

Synonyms: NSC308847,AS1413

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.

Amonafide Chemical Structure

Amonafide Chemical Structure

CAS No. 69408-81-7

Purity & Quality Control

Batch: S136701 DMSO]57 mg/mL]false]Ethanol]4 mg/mL]false]Water]Insoluble]false Purity: 99.94%
99.94

Amonafide Related Products

Signaling Pathway

Topoisomerase Signaling Pathways

Topoisomerase Signaling Pathway

Biological Activity

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.
Targets
Topo II [1]
In vitro
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 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.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01066494 Unknown status
Acute Myeloid Leukemia
Antisoma Research
 January 2010 Phase 2
NCT00273884 Completed
Acute Myeloid Leukemia
Xanthus Pharmaceuticals Inc.
 August 2005 Phase 2
NCT00087854 Completed
Prostate Cancer
Xanthus Pharmaceuticals Inc.
 March 2004 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 283.33 Formula

C16H17N3O2
CAS No. 69408-81-7 SDF Download Amonafide SDF
Smiles CN(C)CCN1C(=O)C2=CC=CC3=CC(=CC(=C32)C1=O)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 57 mg/mL ( (201.17 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 4 mg/mL

Water : Insoluble


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In vivo
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