Catalog No.S1367 Synonyms: NSC308847,AS1413
Molecular Weight(MW): 283.33
Amonafide produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.
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|Description||Amonafide produces protein-associated DNA-strand breaks through a topoisomerase II-mediated reaction, but does not produce topoisomerase I-mediated DNA cleavage. Phase 3.|
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  Amonafide interferes with the DNA breakage-reunion activity of mammalian DNA topoisomerase II resulting in DNA cleavage stimulation.  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.  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.  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.  Amonafide is unaffected by P-glycoprotein-mediated efflux, unlike those of the classical topoisomerase II inhibitors (daunorubicin, doxorubicin, idarubicin, etoposide, and mitoxantrone). 
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-  Hsiang YH, et al. Mol Pharmacol, 1989, 36(3), 371-376.
-  De Isabella P, Nucleic Acids Res, 1995, 23(2), 223-229.
|In vitro||DMSO||57 mg/mL (201.17 mM)|
|Ethanol||4 mg/mL (14.11 mM)|
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