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

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
Structure of AMONAFIDE

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

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

Amonafide L-malate (AS1413, Xanafide) is a DNA intercalator and topoisomerase II inhibitor that induces apoptosis by disrupting chromatin organisation independently of ATP. This is different from classical topoisomerase II inhibitors which induce apoptosis by causing extensive DNA damage. Amonafide L-malate is also able to evade P-glycoprotein and related transporters that contribute to multi-drug resistance. AS1413 had orphan drug status in both the U.S. and the E.U. for the treatment of AML and also received Fast Track status from the U.S. FDA for the treatment of secondary AML. Amonafide L-malate was originated by Xanthus Pharmaceuticals. It was added to Antisoma's pipeline through the acquisition of Xanthus Pharmaceuticals, Inc. in June 2008. Antisoma discontinued development of Amonafide L-malate after data from the open-label, international Phase III ACCEDE trial in over 420 patients showed that 600 mg/m 2 IV amonafide for 5 days plus cytarabine missed the primary endpoint of significantly improving initial remission rate, defined as the proportion of patients who achieve CR or CRi, vs. daunorubicin plus cytarabine.

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
Preclinical antitumor activity of the azonafide series of anthracene-based DNA intercalators.
2001 Mar
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.
2005 Aug 15
Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides.
2008 Feb 15
Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia.
2008 Nov
Overview of naphthalimide analogs as anticancer agents.
2009
Synthesis of new amonafide analogues via coupling reaction and their cytotoxic evaluation and DNA-binding studies.
2009 Jan 15
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
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
Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.
2010 Oct 5
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: in combination with Cytarabine 200 mg/m(2)
600 mg/m(2) over 4 hours on days 1 to 5
Route of Administration: Intravenous
Amonafide displayed significant antitumor activities with IC50 values: 17.96 uM for HL-60, 10.67 uM for HeLa, 11.88 uM for MCF-7, 20.28 uM for LS174 and more than 50 uM for MKN45 cell lines.
Substance Class Chemical
Created
by admin
on Wed Jul 05 22:34:10 UTC 2023
Edited
by admin
on Wed Jul 05 22:34:10 UTC 2023
Record UNII
1Q8D39N37L
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMONAFIDE
INN   MART.   USAN   WHO-DD  
INN   USAN  
Official Name English
amonafide [INN]
Common Name English
3-AMINO-N-(2-(DIMETHYLAMINO)ETHYL)NAPHTHALIMIDE
Common Name English
NAFIDIMIDE
Common Name English
AMONAFIDE [USAN]
Common Name English
AS-1413
Code English
1H-BENZ(DE)ISOQUINOLINE-1,3(2H)-DIONE, 5-AMINO-2-(2-(DIMETHYLAMINO)ETHYL)-
Systematic Name English
AMONAFIDE [MART.]
Common Name English
NSC-308847
Code English
Amonafide [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C582
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
NCI_THESAURUS C1968
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
Code System Code Type Description
RXCUI
1440270
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY RxNorm
USAN
YY-6
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
EPA CompTox
DTXSID30219562
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
CAS
69408-81-7
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
NSC
308847
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
FDA UNII
1Q8D39N37L
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
SMS_ID
100000087427
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
DRUG BANK
DB05022
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
ChEMBL
CHEMBL428676
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
INN
5652
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
NCI_THESAURUS
C71628
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
MESH
C037020
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
EVMPD
SUB05473MIG
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
WIKIPEDIA
Amonafide
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
PUBCHEM
50515
Created by admin on Wed Jul 05 22:34:10 UTC 2023 , Edited by admin on Wed Jul 05 22:34:10 UTC 2023
PRIMARY
Related Record Type Details
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC