AMONAFIDE L-MALATE

Investigational

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 Search

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

Description
Sources: https://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/22272701https://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/21532886

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20170164 \| https://www.ncbi.nlm.nih.gov/pubmed/17826829	Inhibitor 8504
DNA 282 Target ID: CHEMBL3140325 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2550774	Interacts 323

Conditions

Condition	Modality	Highest Phase	Product
Secondary acute myeloid leukemia 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25732165	Primary	Phase III 665	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7977172	Primary	Phase II 1147	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9816035	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8689426/	900 mg/m² 1 times / day multiple, intravenous dose: 900 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		NSC308847 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
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	Analyte	Population
1310.6 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8689426/	900 mg/m² 1 times / day multiple, intravenous dose: 900 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NSC308847 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE 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
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

T_1/2

Value	Dose	Analyte	Population
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8689426/	900 mg/m² 1 times / day multiple, intravenous dose: 900 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NSC308847 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE 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
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

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: https://pubmed.ncbi.nlm.nih.gov/1988134	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1988134	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: https://pubmed.ncbi.nlm.nih.gov/1988134
1104 mg/m2 single, intravenous Studied dose Dose: 1104 mg/m2 Route: intravenous Route: single Dose: 1104 mg/m2 Sources: https://pubmed.ncbi.nlm.nih.gov/2549205	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2549205	DLT: Granulocytopenia... Dose limiting toxicities: Granulocytopenia (grade 4, 40%) Sources: https://pubmed.ncbi.nlm.nih.gov/2549205

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: https://pubmed.ncbi.nlm.nih.gov/1988134	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1988134
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: https://pubmed.ncbi.nlm.nih.gov/1988134	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1988134
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: https://pubmed.ncbi.nlm.nih.gov/1988134	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1988134
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: https://pubmed.ncbi.nlm.nih.gov/1988134	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1988134
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: https://pubmed.ncbi.nlm.nih.gov/2549205	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2549205

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P006083	https://www.1pchem.com/search?query=1P006083
AChemBlock	10263	http://www.achemblock.com/catalogsearch/result/?q=10263
AK Scientific	K157	https://aksci.com/item_detail.php?cat=K157
Angene	AGN-PC-07Y4AQ	http://www.angenechemical.com/productshow/AGN-PC-07Y4AQ.html
ApexBio Technology	A2782	https://www.apexbt.com/catalogsearch/result/?q=A2782
AstaTech	42091	http://astatechinc.com/CPSResult.php?CRNO=42091
BLD Pharm	BD114215	http://www.bldpharm.com/search/Search.html?keyword=BD114215
BOC Sciences	69408-81-7	http://www.bocsci.com/description.asp?cas=69408-81-7
Capot Chemical	22415	https://www.capotchem.com/search.do?q=22415
Chem Scene	CS-0496	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0496
ChemShuttle	141386	https://www.chemshuttle.com/catalogsearch/result/?q=141386
eMolecules	6842649	https://orderbb.emolecules.com/search/#?query=6842649
eNovation Chemicals	D371073	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D371073&searchbtn.x=0&searchbtn.y=0
Hairui	HR111031	http://www.hairuichem.com/en/product/search.do?q=HR111031
KeyOrganics	AS-56124	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-56124
Lab Network	LN01267291	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01267291
mcule	MCULE-5020922694	https://mcule.com/MCULE-5020922694/
MedChem Express	HY-10982	https://www.medchemexpress.com/search.html?q=HY-10982&ft=&fa=&fp=
Molnova	M15655	https://www.molnova.com/en/serch-list.html?keywords=M15655
MolPort	MolPort-005-942-714	https://www.molport.com/shop/molecule-link/MolPort-005-942-714
MolPort	MolPort-046-594-377	https://www.molport.com/shop/molecule-link/MolPort-046-594-377
MuseChem	I002243	https://www.musechem.com/product/I002243.html
MuseChem	I004608	https://www.musechem.com/product/I004608.html
MuseChem	R012133	https://www.musechem.com/product/R012133.html
ShangHai Biochempartner	BCP000198	http://www.biochempartner.com/search_BCP000198
ShangHai Biochempartner	BCP01940	http://www.biochempartner.com/search_BCP01940
Synchem UG and Co KG	fd013	https://www.synchem.de/?s=fd013&post_type=product
TargetMol	T6336	https://www.targetmol.com/search?keyword=T6336
Toronto Research Chemicals	A634205	https://www.trc-canada.com/product-detail/?CatNum=A634205
Vesino Industrial Co Ltd	VA10270	http://www.vsnchem.com/search.do?a=s&psize=20&q=VA10270

PubMed

Title	Date	PubMed
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.	2015-04-10	25732165
Amonafide: a potential role in treating acute myeloid leukemia.	2011-07	21591994
6-Nitro-2-(3-hydroxypropyl)-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis.	2010-12-31	21194464
B1, a novel amonafide analogue, overcomes the resistance conferred by Bcl-2 in human promyelocytic leukemia HL60 cells.	2010-12	21076048
Selective and sensitive detection and quantification of arylamine N-acetyltransferase 2 by a ratiometric fluorescence probe.	2010-10-14	20798904
Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations.	2010-10-05	20923563
5-Butyl-amino-2-[2-(dimethyl-amino)eth-yl]-1H-benz[de]isoquinoline-1,3(2H)-dione.	2010-05-26	21579523
Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights.	2010-04-23	20416083
Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.	2010-04	19748672
A new class of naphthalimide-based antitumor agents that inhibit topoisomerase II and induce lysosomal membrane permeabilization and apoptosis.	2010-03-25	20170164
Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells.	2009-11	19881958
Novel naphthalimide derivatives as potential apoptosis-inducing agents: design, synthesis and biological evaluation.	2009-11	19643513
M(2)-A induces apoptosis and G(2)-M arrest via inhibiting PI3K/Akt pathway in HL60 cells.	2009-10-08	19435648
[Synthesis and in vitro cytotoxicity of naphthalimide polyamine conjugates as antitumor agents].	2009-07	19806915
Synthesis of new amonafide analogues via coupling reaction and their cytotoxic evaluation and DNA-binding studies.	2009-01-15	19070496
Overview of naphthalimide analogs as anticancer agents.	2009	19929786
Naphthalimides and azonafides as promising anti-cancer agents.	2009	19355879
Existing and emerging therapeutic options for the treatment of acute myeloid leukemia.	2008-11	19205108
Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia.	2008-11	18418409
UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.	2008-06	18516294
Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux.	2008-03	17826829
Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides.	2008-02-15	18061459
Synthesis and anticancer activities of 6-amino amonafide derivatives.	2008-01	18043127
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.	2007-08-23	17658777
Molecular design, chemical synthesis, and biological evaluation of '4-1' pentacyclic aryl/heteroaryl-imidazonaphthalimides.	2007-08-01	17532640
Comparative analysis of xanafide cytotoxicity in breast cancer cell lines.	2007-07-02	17551498
Ethonafide-induced cytotoxicity is mediated by topoisomerase II inhibition in prostate cancer cells.	2007-06	17351106
R16, a novel amonafide analogue, induces apoptosis and G2-M arrest via poisoning topoisomerase II.	2007-02	17308047
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.	2005-08-15	15925513
Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations from QM/MM simulations.	2005-06-22	15954791
Statistical method for evaluation of dissolution stability in the formulation development of solid dosage forms: tablets of amonafide.	2004-07	15296092
New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties.	2004-03-11	14998328
[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].	2003-03-04	12611196
Phase II trial of amonafide in central nervous system tumors: a Southwest Oncology Group study.	2002-02	12003186
Naphthalimides as anti-cancer agents: synthesis and biological activity.	2001-11	12678756
Atp-bound topoisomerase ii as a target for antitumor drugs.	2001-05-11	11278845
Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan.	2001-04	11259359
Preclinical antitumor activity of the azonafide series of anthracene-based DNA intercalators.	2001-03	11290869
Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.	1984-08	6091540

Patents

Sample Use Guides

In Vivo Use Guide

600 mg/m(2) over 4 hours on days 1 to 5

Route of Administration: Intravenous

In Vitro Use Guide

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 `Mon Mar 31 20:54:26 GMT 2025` Edited by `admin` on `Mon Mar 31 20:54:26 GMT 2025`
Record UNII	LI06Q37TEG
Record Status	`Validated (UNII)`
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Name

Type

Language

AMONAFIDE L-MALATE

Official Name

English

AMONAFIDE MALATE

Preferred 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

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