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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H17N3O2.C4H6O5
Molecular Weight 417.4125
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMONAFIDE L-MALATE

SMILES

O[C@@H](CC(O)=O)C(O)=O.CN(C)CCN1C(=O)C2=CC=CC3=CC(N)=CC(C1=O)=C23

InChI

InChIKey=JNZBHHQBPHSOMU-WNQIDUERSA-N
InChI=1S/C16H17N3O2.C4H6O5/c1-18(2)6-7-19-15(20)12-5-3-4-10-8-11(17)9-13(14(10)12)16(19)21;5-2(4(8)9)1-3(6)7/h3-5,8-9H,6-7,17H2,1-2H3;2,5H,1H2,(H,6,7)(H,8,9)/t;2-/m.0/s1

HIDE SMILES / InChI

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

Molecular Formula C4H6O5
Molecular Weight 134.0874
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.
1984 Aug
Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan.
2001 Apr
Preclinical antitumor activity of the azonafide series of anthracene-based DNA intercalators.
2001 Mar
Atp-bound topoisomerase ii as a target for antitumor drugs.
2001 May 11
Naphthalimides as anti-cancer agents: synthesis and biological activity.
2001 Nov
Phase II trial of amonafide in central nervous system tumors: a Southwest Oncology Group study.
2002 Feb
[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
New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties.
2004 Mar 11
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.
2005 Aug 15
Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations from QM/MM simulations.
2005 Jun 22
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
Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides.
2008 Feb 15
Synthesis and anticancer activities of 6-amino amonafide derivatives.
2008 Jan
UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.
2008 Jun
Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux.
2008 Mar
Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia.
2008 Nov
Existing and emerging therapeutic options for the treatment of acute myeloid leukemia.
2008 Nov
Overview of naphthalimide analogs as anticancer agents.
2009
Naphthalimides and azonafides as promising anti-cancer agents.
2009
Synthesis of new amonafide analogues via coupling reaction and their cytotoxic evaluation and DNA-binding studies.
2009 Jan 15
[Synthesis and in vitro cytotoxicity of naphthalimide polyamine conjugates as antitumor agents].
2009 Jul
Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells.
2009 Nov
Novel naphthalimide derivatives as potential apoptosis-inducing agents: design, synthesis and biological evaluation.
2009 Nov
M(2)-A induces apoptosis and G(2)-M arrest via inhibiting PI3K/Akt pathway in HL60 cells.
2009 Oct 8
Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.
2010 Apr
Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights.
2010 Apr 23
B1, a novel amonafide analogue, overcomes the resistance conferred by Bcl-2 in human promyelocytic leukemia HL60 cells.
2010 Dec
6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis.
2010 Dec 31
A new class of naphthalimide-based antitumor agents that inhibit topoisomerase II and induce lysosomal membrane permeabilization and apoptosis.
2010 Mar 25
5-Butyl-amino-2-[2-(dimethyl-amino)eth-yl]-1H-benz[de]isoquinoline-1,3(2H)-dione.
2010 May 26
Selective and sensitive detection and quantification of arylamine N-acetyltransferase 2 by a ratiometric fluorescence probe.
2010 Oct 14
Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.
2010 Oct 5
Amonafide: a potential role in treating acute myeloid leukemia.
2011 Jul
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
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 Sat Dec 16 01:35:10 GMT 2023
Edited
by admin
on Sat Dec 16 01:35:10 GMT 2023
Record UNII
LI06Q37TEG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMONAFIDE L-MALATE
USAN  
Official Name English
AS1413
Code English
XAN 02
Code English
AMONAFIDE L-MALATE [USAN]
Common Name English
AS 1413
Code English
BUTANEDIOIC ACID, HYDROXY-, (2S)-, COMPD. WITH 5-AMINO-2-(2-(DIMETHYLAMINO)ETHYL)-1H-BENZ(DE)ISOQUINOLINE-1,3(2H)-DIONE (1:1)
Common Name English
AMONAFIDE MALATE
WHO-DD  
Common Name English
Amonafide malate [WHO-DD]
Common Name English
XAN-02
Code English
5-AMINO-2-(2-(DIMETHYLAMINO)ETHYL)-1H-BENZ(DE)ISOQUINOLINE-1,3(2H)-DIONE (2S)-2- YDROXYBUTANEDIOATE
Common Name English
XANAFIDE
Brand Name English
BUTANEDIOIC ACID, 2-HYDROXY-, (2S)-, COMPD. WITH 5-AMINO-2-(2-(DIMETHYLAMINO)ETHYL-1H-BENZ(DE)ISOQUINOLINE-1,3(2H)-DIONE (1:1)
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/07/483
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
FDA ORPHAN DRUG 227506
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
NCI_THESAURUS C582
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
Code System Code Type Description
MESH
C522694
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
NCI_THESAURUS
C61306
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
ChEMBL
CHEMBL428676
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
CAS
618863-54-0
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
PUBCHEM
10216431
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
USAN
YY-61
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
SMS_ID
100000128388
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
FDA UNII
LI06Q37TEG
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
EVMPD
SUB35395
Created by admin on Sat Dec 16 01:35:10 GMT 2023 , Edited by admin on Sat Dec 16 01:35:10 GMT 2023
PRIMARY
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ACTIVE MOIETY