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 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
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.
2005 Aug 15
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
Comparative analysis of xanafide cytotoxicity in breast cancer cell lines.
2007 Jul 2
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 L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia.
2008 Nov
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
Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.
2010 Oct 5
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 Fri Dec 15 15:02:08 GMT 2023
Edited
by admin
on Fri Dec 15 15:02:08 GMT 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 Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
NCI_THESAURUS C1968
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
Code System Code Type Description
RXCUI
1440270
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY RxNorm
USAN
YY-6
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
EPA CompTox
DTXSID30219562
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
CAS
69408-81-7
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
NSC
308847
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
FDA UNII
1Q8D39N37L
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
SMS_ID
100000087427
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
DRUG BANK
DB05022
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
ChEMBL
CHEMBL428676
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
INN
5652
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
NCI_THESAURUS
C71628
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
MESH
C037020
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
EVMPD
SUB05473MIG
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
WIKIPEDIA
Amonafide
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
PUBCHEM
50515
Created by admin on Fri Dec 15 15:02:08 GMT 2023 , Edited by admin on Fri Dec 15 15:02:08 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC