Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H17N3O2.2ClH |
Molecular Weight | 356.247 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.CN(C)CCN1C(=O)C2=CC(N)=CC3=CC=CC(C1=O)=C23
InChI
InChIKey=AEMLYYQEBPJIEO-UHFFFAOYSA-N
InChI=1S/C16H17N3O2.2ClH/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;2*1H
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 |
---|---|---|---|
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 |
---|---|---|---|---|
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 |
---|---|---|---|---|
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 |
---|---|---|
Atp-bound topoisomerase ii as a target for antitumor drugs. | 2001 May 11 |
|
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups. | 2005 Aug 15 |
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Synthesis and anticancer activities of 6-amino amonafide derivatives. | 2008 Jan |
|
Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux. | 2008 Mar |
|
Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia. | 2010 Apr |
|
5-Butyl-amino-2-[2-(dimethyl-amino)eth-yl]-1H-benz[de]isoquinoline-1,3(2H)-dione. | 2010 May 26 |
|
Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia. | 2015 Apr 10 |
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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DTXSID30164467
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C999
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150091-68-2
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177896
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2UAV344O66
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ACTIVE MOIETY
SUBSTANCE RECORD