AMONAFIDE L-MALATE

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://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/21532886https://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/22272701

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

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 8297
DNA 278 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 656	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7977172	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9816035	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 Page: p.936
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 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: https://pubmed.ncbi.nlm.nih.gov/2549205 Page: p.1354	DLT: Granulocytopenia... Dose limiting toxicities: Granulocytopenia (grade 4, 40%) Sources: https://pubmed.ncbi.nlm.nih.gov/2549205 Page: p.1354

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 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/1988134 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: https://pubmed.ncbi.nlm.nih.gov/2549205 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: https://pubmed.ncbi.nlm.nih.gov/2549205 Page: p.1354

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
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
MedChem Express	HY-10982	https://www.medchemexpress.com/search.html?q=HY-10982&ft=&fa=&fp=
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
Molnova	M15655	https://www.molnova.com/en/serch-list.html?keywords=M15655
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
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
mcule	MCULE-5020922694	https://mcule.com/MCULE-5020922694/

PubMed

Title	Date	PubMed
Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan.	2001 Apr	11259359
Preclinical antitumor activity of the azonafide series of anthracene-based DNA intercalators.	2001 Mar	11290869
Atp-bound topoisomerase ii as a target for antitumor drugs.	2001 May 11	11278845
Phase II trial of amonafide in central nervous system tumors: a Southwest Oncology Group study.	2002 Feb	12003186
New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties.	2004 Mar 11	14998328
Novel thiazonaphthalimides as efficient antitumor and DNA photocleaving agents: effects of intercalation, side chains, and substituent groups.	2005 Aug 15	15925513
Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations from QM/MM simulations.	2005 Jun 22	15954791
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	17658777
R16, a novel amonafide analogue, induces apoptosis and G2-M arrest via poisoning topoisomerase II.	2007 Feb	17308047
Ethonafide-induced cytotoxicity is mediated by topoisomerase II inhibition in prostate cancer cells.	2007 Jun	17351106
Antiproliferative effects on human tumor cells and rat aortic smooth muscular cells of 2,3-heteroarylmaleimides and heterofused imides.	2008 Feb 15	18061459
Synthesis and anticancer activities of 6-amino amonafide derivatives.	2008 Jan	18043127
UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers.	2008 Jun	18516294
Amonafide, a topoisomerase II inhibitor, is unaffected by P-glycoprotein-mediated efflux.	2008 Mar	17826829
Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia.	2008 Nov	18418409
Existing and emerging therapeutic options for the treatment of acute myeloid leukemia.	2008 Nov	19205108
Overview of naphthalimide analogs as anticancer agents.	2009	19929786
Naphthalimides and azonafides as promising anti-cancer agents.	2009	19355879
[Synthesis and in vitro cytotoxicity of naphthalimide polyamine conjugates as antitumor agents].	2009 Jul	19806915
Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells.	2009 Nov	19881958
Novel naphthalimide derivatives as potential apoptosis-inducing agents: design, synthesis and biological evaluation.	2009 Nov	19643513
M(2)-A induces apoptosis and G(2)-M arrest via inhibiting PI3K/Akt pathway in HL60 cells.	2009 Oct 8	19435648
Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia.	2010 Apr	19748672
Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights.	2010 Apr 23	20416083
A new class of naphthalimide-based antitumor agents that inhibit topoisomerase II and induce lysosomal membrane permeabilization and apoptosis.	2010 Mar 25	20170164
5-Butyl-amino-2-[2-(dimethyl-amino)eth-yl]-1H-benz[de]isoquinoline-1,3(2H)-dione.	2010 May 26	21579523
Amonafide: a potential role in treating acute myeloid leukemia.	2011 Jul	21591994
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	25732165

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 UTC 2023` Edited by `admin` on `Sat Dec 16 01:35:10 UTC 2023`
Record UNII	LI06Q37TEG
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMONAFIDE L-MALATE

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

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