Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H17N3O2 |
Molecular Weight | 283.3251 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)CCN1C(=O)C2=CC(N)=CC3=CC=CC(C1=O)=C23
InChI
InChIKey=UPALIKSFLSVKIS-UHFFFAOYSA-N
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
DescriptionSources: https://adisinsight.springer.com/drugs/800020664 | http://www.io.nihr.ac.uk/wp-content/uploads/migrated/1560.9e11b231899b3bee8fba1e90fc9fd6cd.pdf | https://www.rdmag.com/news/2010/09/antisomas-phase-iii-trial-as1413-completes-patient-enrolment | https://www.ncbi.nlm.nih.gov/pubmed/21532886https://www.ncbi.nlm.nih.gov/pubmed/21591994 | https://www.ncbi.nlm.nih.gov/pubmed/17826829 | https://www.ncbi.nlm.nih.gov/pubmed/25732165 | https://www.ncbi.nlm.nih.gov/pubmed/7977172 | https://www.ncbi.nlm.nih.gov/pubmed/9816035 | https://www.ncbi.nlm.nih.gov/pubmed/22272701
Sources: https://adisinsight.springer.com/drugs/800020664 | http://www.io.nihr.ac.uk/wp-content/uploads/migrated/1560.9e11b231899b3bee8fba1e90fc9fd6cd.pdf | https://www.rdmag.com/news/2010/09/antisomas-phase-iii-trial-as1413-completes-patient-enrolment | https://www.ncbi.nlm.nih.gov/pubmed/21532886https://www.ncbi.nlm.nih.gov/pubmed/21591994 | https://www.ncbi.nlm.nih.gov/pubmed/17826829 | https://www.ncbi.nlm.nih.gov/pubmed/25732165 | https://www.ncbi.nlm.nih.gov/pubmed/7977172 | https://www.ncbi.nlm.nih.gov/pubmed/9816035 | https://www.ncbi.nlm.nih.gov/pubmed/22272701
Amonafide is an imide derivative of naphthalic acid. It is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA. Amonafide retains cytotoxic activity even in the presence of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR). It is a new investigational anticancer drug. Amonafide has been extensively studied in patients with malignant solid tumors, like prostate cancer, breast cancer and others. When its usefulness in the treatment of various solid malignancies proved limited, focus was shifted to establishing its use as an antileukemic agent, specifically against secondary and treatment-associated acute myeloid leukemia (AML).
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3349561 | https://www.ncbi.nlm.nih.gov/pubmed/7623074
Curator's Comment: poor penetration. brain retained less than 0.02% of the original dose.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2094255 |
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Target ID: CHEMBL3140325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2550774 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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3.25 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2549205 |
1104 mg/m² single, intravenous dose: 1104 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
AMONAFIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
16.64 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2549205 |
1104 mg/m² single, intravenous dose: 1104 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
AMONAFIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
40 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1988134 |
1800 mg/m² 1 times / day multiple, intravenous dose: 1800 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
AMONAFIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2549205 |
1104 mg/m² single, intravenous dose: 1104 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: |
AMONAFIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
5.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1988134 |
1800 mg/m² 1 times / day multiple, intravenous dose: 1800 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: |
AMONAFIDE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1800 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1800 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1800 mg/m2, 1 times / day Sources: Page: p.936 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.936 |
DLT: Mucositis, Skin erythema... Other AEs: Nausea, Vomiting... Dose limiting toxicities: Mucositis (100%) Other AEs:Skin erythema (100%) Nausea (grade 3, 50%) Sources: Page: p.936Vomiting (grade 3, 50%) |
1104 mg/m2 single, intravenous Studied dose Dose: 1104 mg/m2 Route: intravenous Route: single Dose: 1104 mg/m2 Sources: Page: p.1354 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.1354 |
DLT: Granulocytopenia... Dose limiting toxicities: Granulocytopenia (grade 4, 40%) Sources: Page: p.1354 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Mucositis | 100% DLT |
1800 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1800 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1800 mg/m2, 1 times / day Sources: Page: p.936 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.936 |
Skin erythema | 100% DLT |
1800 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1800 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1800 mg/m2, 1 times / day Sources: Page: p.936 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.936 |
Nausea | grade 3, 50% | 1800 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1800 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1800 mg/m2, 1 times / day Sources: Page: p.936 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.936 |
Vomiting | grade 3, 50% | 1800 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 1800 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 1800 mg/m2, 1 times / day Sources: Page: p.936 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.936 |
Granulocytopenia | grade 4, 40% DLT |
1104 mg/m2 single, intravenous Studied dose Dose: 1104 mg/m2 Route: intravenous Route: single Dose: 1104 mg/m2 Sources: Page: p.1354 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.1354 |
PubMed
Title | Date | PubMed |
---|---|---|
Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e. | 1984 Aug |
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Preclinical antitumor activity of the azonafide series of anthracene-based DNA intercalators. | 2001 Mar |
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Atp-bound topoisomerase ii as a target for antitumor drugs. | 2001 May 11 |
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Molecular design, chemical synthesis, and biological evaluation of '4-1' pentacyclic aryl/heteroaryl-imidazonaphthalimides. | 2007 Aug 1 |
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Overview of naphthalimide analogs as anticancer agents. | 2009 |
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Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells. | 2009 Nov |
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A new class of naphthalimide-based antitumor agents that inhibit topoisomerase II and induce lysosomal membrane permeabilization and apoptosis. | 2010 Mar 25 |
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Selective and sensitive detection and quantification of arylamine N-acetyltransferase 2 by a ratiometric fluorescence probe. | 2010 Oct 14 |
Sample Use Guides
In Vivo Use Guide
Sources: http://www.io.nihr.ac.uk/wp-content/uploads/migrated/1560.9e11b231899b3bee8fba1e90fc9fd6cd.pdf
Curator's Comment: in combination with Cytarabine 200 mg/m(2)
Amonafide L-malate is administered as an intravenous infusion (IV) at 600mg/m2 daily, over 5 days in combination with cytarabine.
Route of Administration:
Intravenous
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C582
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NCI_THESAURUS |
C1968
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1440270
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YY-6
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DTXSID30219562
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69408-81-7
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308847
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1Q8D39N37L
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100000087427
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DB05022
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CHEMBL428676
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5652
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C71628
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C037020
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SUB05473MIG
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Amonafide
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50515
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ACTIVE MOIETY
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)