Home DNA Damage/DNA Repair Topoisomerase inhibitor Amonafide

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Amonafide Topoisomerase inhibitor

Cat.No.S1367

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 Topoisomerase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 283.33

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Quality Control

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

Chemical Information, Storage & Stability

Molecular Weight 283.33 Formula

C16H17N3O2

 Storage (From the date of receipt)
CAS No. 69408-81-7 Download SDF Storage of Stock Solutions

Synonyms NSC308847,AS1413 Smiles CN(C)CCN1C(=O)C2=CC=CC3=CC(=CC(=C32)C1=O)N

Solubility

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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Mechanism of Action

Targets/IC50/Ki
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. This compound treatment inhibits colony formation of the leukemic cell lines and the normal human bone marrow GM-CFC in a dose-dependent manner. It does not produce topoisomerase I-mediated DNA cleavage even at 100 μM. The m-AMSA-resistant line is less than 2-fold resistant to this compound [1] This chemical 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, this compound-stimulated cleavage intensity patterns are markedly different. It 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 this agent is affected only slightly (less than 3-fold) by 1 mM ATP, suggesting that it is an ATP-insensitive topoisomerase II inhibitor in contrast to doxorubicin, etoposide, and mitoxantrone. [4] This compound 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] It is unaffected by P-glycoprotein-mediated efflux, unlike those of the classical topoisomerase II inhibitors (daunorubicin, doxorubicin, idarubicin, etoposide, and mitoxantrone). [6]
References
  • https://pubmed.ncbi.nlm.nih.gov/11278845/
  • https://pubmed.ncbi.nlm.nih.gov/14998328/
  • https://pubmed.ncbi.nlm.nih.gov/17826829/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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