U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of AMONAFIDE DIHYDROCHLORIDE

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

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C16H17N3O2
Molecular Weight 283.3251
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

Curator's Comment: poor penetration. brain retained less than 0.02% of the original dose.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.25 μg/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
16.64 μg × h/mL
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
6.7 h
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
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

Doses

DosePopulationAdverse 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%)
Skin erythema (100%)
Other AEs:
Nausea (grade 3, 50%)
Vomiting (grade 3, 50%)
Sources: Page: p.936
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

AEs

AESignificanceDosePopulation
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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Atp-bound topoisomerase ii as a target for antitumor drugs.
2001 May 11
[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].
2002 Sep-Oct
Statistical method for evaluation of dissolution stability in the formulation development of solid dosage forms: tablets of amonafide.
2004 Jul
Molecular design, chemical synthesis, and biological evaluation of '4-1' pentacyclic aryl/heteroaryl-imidazonaphthalimides.
2007 Aug 1
2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a novel nonhematotoxic naphthalimide derivative with potent antitumor activity.
2007 Aug 23
R16, a novel amonafide analogue, induces apoptosis and G2-M arrest via poisoning topoisomerase II.
2007 Feb
Comparative analysis of xanafide cytotoxicity in breast cancer cell lines.
2007 Jul 2
Ethonafide-induced cytotoxicity is mediated by topoisomerase II inhibition in prostate cancer cells.
2007 Jun
Existing and emerging therapeutic options for the treatment of acute myeloid leukemia.
2008 Nov
Overview of naphthalimide analogs as anticancer agents.
2009
B1, a novel amonafide analogue, overcomes the resistance conferred by Bcl-2 in human promyelocytic leukemia HL60 cells.
2010 Dec
Selective and sensitive detection and quantification of arylamine N-acetyltransferase 2 by a ratiometric fluorescence probe.
2010 Oct 14
Amonafide: a potential role in treating acute myeloid leukemia.
2011 Jul
Patents

Sample Use Guides

In Vivo Use Guide
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
Amonafide significantly inhibits the growth of HT-29, HeLa, and PC3 cells with IC50 of 4.67 uM, 2.73 uM, and 6.38 uM, respectively
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:09:11 GMT 2023
Edited
by admin
on Fri Dec 15 17:09:11 GMT 2023
Record UNII
2UAV344O66
Record Status Validated (UNII)
Record Version
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Name Type Language
AMONAFIDE DIHYDROCHLORIDE
WHO-DD  
Common Name English
AMONAFIDE HYDROCHLORIDE
MART.  
Common Name English
QUINAMED
Brand Name English
Amonafide dihydrochloride [WHO-DD]
Common Name English
1H-BENZ(DE)ISOQUINOLINE-1,3(2H)-DIONE, 5-AMINO-2-(2-(DIMETHYLAMINO)ETHYL)-, HYDROCHLORIDE (1:2)
Systematic Name English
3-AMINO-N-(2-(DIMETHYLAMINO)ETHYL)NAPHTHALIMIDE HYDROCHLORIDE
Common Name English
AMONAFIDE HYDROCHLORIDE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C582
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
NCI_THESAURUS C1968
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID30164467
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
PRIMARY
NCI_THESAURUS
C999
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
PRIMARY
CAS
150091-68-2
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
PRIMARY
PUBCHEM
177896
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
PRIMARY
FDA UNII
2UAV344O66
Created by admin on Fri Dec 15 17:09:11 GMT 2023 , Edited by admin on Fri Dec 15 17:09:11 GMT 2023
PRIMARY
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