DEXRAZOXANE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H16N4O4
Molecular Weight	268.2691
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](CN1CC(=O)NC(=O)C1)N2CC(=O)NC(=O)C2

InChI

InChIKey=BMKDZUISNHGIBY-ZETCQYMHSA-N

InChI=1S/C11H16N4O4/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19)/t7-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19536310
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf

Dexrazoxane is a cardioprotective drug used in patients with breast cancer to reduce cardiomyopathy associated with doxorubicin administration. Dexrazoxane is believed to act by two mechanisms: it inhibits DNA topoisomerase II and acts as a chelator for iron ions.

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/19536310	Inhibitor 8297		13.0 µM [IC50]
Iron 18 Target ID: CHEMBL2363058 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	Chelating Agent 142		17.4 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	Secondary		Approved 8429	ZINECARD Approved Use Zinecard is indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control. Launch Date 1995

C_max

Value	Dose	Co-administered	Analyte	Population
337 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29273587	60 mg/kg single, intraperitoneal dose: 60 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		DEXRAZOXANE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
838 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29273587	60 mg/kg single, intraperitoneal dose: 60 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		DEXRAZOXANE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	500 mg/m² single, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: DOXORUBICIN	DOXORUBICIN	DEXRAZOXANE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29273587	60 mg/kg single, intraperitoneal dose: 60 mg/kg route of administration: Intraperitoneal experiment type: SINGLE co-administered:		DEXRAZOXANE plasma	Oryctolagus cuniculus population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	500 mg/m² single, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: DOXORUBICIN	DOXORUBICIN	DEXRAZOXANE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
250 mg/m2 1 times / 4 weeks multiple, intravenous (total) MTD Dose: 250 mg/m2, 1 times / 4 weeks Route: intravenous Route: multiple Dose: 250 mg/m2, 1 times / 4 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/11410492/	unhealthy, 57 years (range: 46-76 years) n = 22 Health Status: unhealthy Condition: advanced malignancies Age Group: 57 years (range: 46-76 years) Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/11410492/	Disc. AE: Thrombocytopenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (grade 4, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/11410492/
900 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 900 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 900 mg/m2, 1 times / 3 weeks Co-administed with:: doxorubicin(60 mg/m^2; 1/3 week) Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/	unhealthy, adult n = 6 Health Status: unhealthy Condition: advanced malignancies Age Group: adult Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/
600 mg/m2 1 times / 3 weeks multiple, intravenous RP2D Dose: 600 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 600 mg/m2, 1 times / 3 weeks Co-administed with:: doxorubicin(60 mg/m^2; 1/3 week) Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/	unhealthy, adult n = 9 Health Status: unhealthy Condition: advanced malignancies Age Group: adult Sex: M+F Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/	DLT: Neutropenia... Dose limiting toxicities: Neutropenia (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1433357/
500 mg/m2 1 times / day multiple, intravenous Recommended Dose: 500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 500 mg/m2, 1 times / day Co-administed with:: doxorubicin(50 mg/m^2) fluorouracil cyclophosphamide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	unhealthy, adult n = 102 Health Status: unhealthy Condition: breast cancer Age Group: adult Sex: F Population Size: 102 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	Other AEs: Alopecia, Nausea... Other AEs: Alopecia (100%) Nausea (51%) Vomiting (42%) Malaise and fatigue (48%) Anorexia (27%) Stomatitis (26%) Fever (22%) Infection (19%) Diarrhea (14%) Injection site pain (13%) Sepsis (12%) Neurotoxicity (10%) Erythema (4%) Phlebitis (3%) Esophagitis (3%) Hemorrhage (3%) Extravasation (3%) Urticaria (2%) Administration site recall reaction (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf
500 mg/m2 1 times / day multiple, intravenous Recommended Dose: 500 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 500 mg/m2, 1 times / day Co-administed with:: doxorubicin(50 mg/m^2) fluorouracil cyclophosphamide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	unhealthy, adult n = 413 Health Status: unhealthy Condition: breast cancer Age Group: adult Sex: F Population Size: 413 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf	Other AEs: Alopecia, Nausea... Other AEs: Alopecia (94%) Nausea (77%) Vomiting (59%) Malaise and fatigue (61%) Anorexia (42%) Stomatitis (34%) Fever (34%) Infection (23%) Diarrhea (21%) Injection site pain (12%) Sepsis (17%) Neurotoxicity (17%) Erythema (5%) Phlebitis (6%) Esophagitis (6%) Dysphagia (8%) Hemorrhage (2%) Extravasation (1%) Urticaria (2%) Administration site recall reaction (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020212s017lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1307	http://www.3bsc.com/index/pro_info.php?id=55023
AA Blocks	AA002OL7	https://www.aablocks.com/goods/Goods/detail?id=AA002OL7
AEchem Scientific Corp., USA	AE1-014835	http://www.aechemsc.com/info_products/AE1-014835.php
AHH Chemical co.,ltd	MT-49873	http://www.ahhchemical.com/product/MT-49873.html
AK Scientific, Inc. (AKSCI)	69488	http://www.aksci.com/item_detail.php?cat=69488
AK Scientific, Inc. (AKSCI)	J90038	http://www.aksci.com/item_detail.php?cat=J90038
Aaron Chemicals	AR002PCZ	http://www.aaronchem.com/24584-09-6
Acadechem	ACDS-062689	http://www.acadechemical.com/product/137388
Achemo Scientific Limited	AC-74299	http://www.achemo.com/search/?Keyword= 24584-09-6
Achemtek	0104-020754	http://www.achemtek.com/24584-09-6
Alfa Chemistry	AP24584096	https://reagents.alfa-chemistry.com/product/dexrazoxane-cas-24584-09-6-8513.html
Ambinter	Amb22744843	http://www.ambinter.com/reference/22744843
Angene	AGN-PC-0O877E	http://www.angenechemical.com/productshow/AGN-PC-0O877E.html
Anward	ANW-44923	http://www.anward.com/pro_result/31374
ApexBio Technology	A1602	http://www.apexbt.com/dexrazoxane-hcl-icrf-187-adr-529.html
AstaTech, Inc.	25916	http://www.astatechinc.com/CPSResult.php?CRNO=29109
Aurora Fine Chemicals LLC	A17.905.381	http://online.aurorafinechemicals.com/info?ID=A17.905.381
Aurum Pharmatech LLC	MP-0159	http://www.Aurumpharmatech.com/Product/ProductDetails/MP_0159
AvaChem Scientific	3082B	http://www.avachem.com/productSearch.asp?3082B
Avantor Inc	TCD4227-100MG	https://us.vwr.com/store/product/16811739/dexrazoxane-98-0-by-titrimetric-analysis
BLD Pharm	BD123889	http://www.bldpharm.com/products/24584-09-6.html
BioSynth	J-015579	https://www.biosynth.com/en/products/all-products/products/J-015579.html
BioSynth	J-520219	https://www.biosynth.com/en/products/all-products/products/J-520219.html
CSNpharm	CSN10785	https://www.csnpharm.com/products/dexrazoxane.html
Chem Scene	CS-2769	http://www.chemscene.com/24584-09-6.html
ChemMol	49408757	http://www.chemmol.com/chemmol/49408757.html
Chemenu	CM120112	http://www.chemenu.com/products/CM120112
Chemspace	CSSB00000054680	https://chem-space.com/CSSB00000054680
DAOGE BIOPHARMA	DG21-14309	https://www.daogechem.com/product/24584-09-6.html
Glentham Life Sciences	GP2739	http://www.glentham.com/products/product/GP2739/
Huateng Pharma	F80010873	http://en.huatengsci.com/product/Dexrazoxane.html
Lab Network	LN00337707	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00337707
Matrix Scientific	126235	https://www.matrixscientific.com/126235.html
MedChem Express	HY-B0581	https://www.medchemexpress.com/dexrazoxane.html
MuseChem	I002831	https://www.musechem.com/product/I002831.html
OChem	6570	http://www.ocheminc.com/index.php?act=psearch&pid=584D096
Oakwood	93447	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=78621&ExtHyperLink=1
Parchem	28706	http://www.parchem.com/chemical-supplier-distributor/Dexrazoxane-018706.aspx
Renno Tech	RP29555	http://www.rennotech.com/product_show.asp?id=35162
Sigma-Aldrich	05587_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/05587?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	D1446_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/d1446?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S047032	http://www.sinfoobiotech.com/product/1050430
Smolecule	S548609	http://www.smolecule.com/products/s548609
TCI (Tokyo Chemical Industry)	D4227	http://www.tcichemicals.com/eshop/en/us/commodity/D4227/index.html
THE BioTek	bt-288014	https://www.thebiotek.com/product/inhibitors/bt-288014
Yuhao Chemical	LT4788	http://www.chemyuhao.com/24584-09-6.html
abcr GmbH	AB436257	http://www.abcr.com/shop/en/AB436257
eNovation Chemicals	D672527	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672527
eNovation Chemicals	D764439	https://www.enovationchem.com/ProductDetails.asp?ProductID=D764439
eNovation Chemicals	Y0980546	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0980546
iChemical	EBD45155	http://www.ichemical.com/products/24584-09-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Protection against acute adriamycin-induced cardiotoxicity by garlic: role of endogenous antioxidants and inhibition of TNF-alpha expression.	2003 Dec 20	14687418
Protein profiling in daunorubicin-induced cardiomyopathy.	2003 Sep	14986890
Iron chelators in cancer chemotherapy.	2004	15579100
Synthesis and characterization of the biological activity of the cisplatin analogs, cis-PtCl(2)(dexrazoxane) and cis-PtCl(2)(levrazoxane), of the topoisomerase II inhibitors dexrazoxane (ICRF-187) and levrazoxane (ICRF-186).	2004 Apr	15041241
Cardiotoxicity of cytotoxic drugs.	2004 Apr	15023436
Characterisation of cytotoxicity and DNA damage induced by the topoisomerase II-directed bisdioxopiperazine anti-cancer agent ICRF-187 (dexrazoxane) in yeast and mammalian cells.	2004 Dec 2	15575955
Antitumor effects of two bisdioxopiperazines against two experimental lung cancer models in vivo.	2004 Dec 24	15617579
Mitoxantrone treatment of multiple sclerosis: safety considerations.	2004 Dec 28	15623667
Anaphylaxis to dexrazoxane (ICRF-187) following three previous uncomplicated infusions.	2004 Feb	14763950
The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.	2004 Jul 8	15247354
[Dexrazoxane in patients with B-lymphomas or acute leukemias in the 2nd complete remission enables further therapy with cardiotoxic anthracyclines over recommended cumulative doses].	2004 Jun	15346637
[Dexrazoxane and cardiotoxicity in repeatedly treated patients].	2004 Jun	15346632
Rabbit model for in vivo study of anthracycline-induced heart failure and for the evaluation of protective agents.	2004 Jun	15182761
Dexrazoxane for anthracycline extravasation and GM-CSF for skin ulceration and wound healing.	2004 May	15120669
Can dexrazoxane reduce myocardial injury in anthracycline-treated children with acute lymphoblastic leukemia?	2004 Nov	16264791
[Cardiac prevention: the oncologic point of view].	2004 Nov	15899627
Evaluating the role of dexrazoxane as a cardioprotectant in cancer patients receiving anthracyclines.	2004 Nov	15531396
The iron chelating cardioprotective prodrug dexrazoxane does not affect the cell growth inhibitory effects of bleomycin.	2004 Nov	15522409
Concurrent therapies that protect against doxorubicin-induced cardiomyopathy.	2004 Oct	15515283
Accelerated approval of oncology products: a decade of experience.	2004 Oct 20	15494600
Feasibility and pharmacokinetic study of infusional dexrazoxane and dose-intensive doxorubicin administered concurrently over 96 h for the treatment of advanced malignancies.	2004 Sep	15173955
The prevention and management of cardiovascular complications of chemotherapy in patients with cancer.	2005	15984906
Dexrazoxane : a review of its use for cardioprotection during anthracycline chemotherapy.	2005	15892593
Anthracycline-induced cardiotoxicity in children with cancer: strategies for prevention and management.	2005	15871628
Myocardial content of selected elements in experimental anthracycline-induced cardiomyopathy in rabbits.	2005 Apr	15954742
Molecular pharmacology of the interaction of anthracyclines with iron.	2005 Aug	15883202
Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients.	2005 Dec	16325366
Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography.	2005 Dec	16035077
The antitumor anthracyclines doxorubicin and daunorubicin do not inhibit cell growth through the formation of iron-mediated reactive oxygen species.	2005 Jan	15613911
Cardioprotective interventions for cancer patients receiving anthracyclines.	2005 Jan 25	15674919
Monitoring cardiac function in patients receiving doxorubicin.	2005 Jul	16098293
CD95/Apo-1/Fas: independent cell death induced by doxorubicin in normal cultured cardiomyocytes.	2005 Jul	15703961
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Metabolism of the cardioprotective drug dexrazoxane and one of its metabolites by isolated rat myocytes, hepatocytes, and blood.	2005 Jun	15764716
Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients.	2005 Jun 15	15700251
Gender-dependent reductions in vertebrae length, bone mineral density and content by doxorubicin are not reduced by dexrazoxane in young rats: effect on growth plate and intervertebral discs.	2005 Mar	15570399
Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin.	2005 May 15	15897593
Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients.	2005 Nov	16044276
Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas.	2005 Oct 1	16192597
Amifostine and dexrazoxane enhance the rapid loss of bone mass and further deterioration of vertebrae architecture in female rats.	2005 Sep	16151678
Metabolism of the one-ring open metabolites of the cardioprotective drug dexrazoxane to its active metal-chelating form in the rat.	2005 Sep	15980099
Combining etoposide and dexrazoxane synergizes with radiotherapy and improves survival in mice with central nervous system tumors.	2005 Sep 15	16166453
Clinical nurse specialist and evidence-based practice: managing anthracycline extravasation.	2005 Sep-Oct	16079361
Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy.	2006 Apr	16423847
Altered responsiveness of the guinea-pig isolated ileum to smooth muscle stimulants and to electrical stimulation after in situ ischemia.	2006 Feb	16341232
Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up.	2006 Feb	16034614
Matrix metalloproteinase-2 and -9 are induced differently by doxorubicin in H9c2 cells: The role of MAP kinases and NAD(P)H oxidase.	2006 Feb 15	16213474
Experimental study of dexrazoxane-anthracycline combinations using the model of isolated perfused rat heart.	2006 Feb 8	16129573
Suppression of mitoxantrone cardiotoxicity in multiple sclerosis patients by dexrazoxane.	2006 Jan	16374818
Treatment of anthracycline extravasation in mice with dexrazoxane with or without DMSO and hydrocortisone.	2006 Jan	16001176

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage ratio of dexrazoxane to doxorubicin is 10:1 (e.g., 500 mg/m2 dexrazoxane to 50 mg/m2 doxorubicin). Do not administer doxorubicin before dexrazoxane.

Route of Administration: Intravenous

In Vitro Use Guide

Human osteoblasts P2 cells and Human ginigiva fibroblasts P2 cells were treated with zoledronic acid (50 umol/L) and the cytoprotectant dexrazoxane (600 umol/L). At that concentration dexrazoxane showed significant cytoprotective effect.

Name

Type

Language

DEXRAZOXANE

Official Name

English

(+)-1,2-BIS(3,5-DIOXOPIPERAZIN-1-YL)PROPANE

Systematic Name

English

Dexrazoxane [WHO-DD]

Common Name

English

dexrazoxane [INN]

Common Name

English

DEXRAZOXANE [USAN]

Common Name

English

RAZOXANE, (S)-

Common Name

English

RAZOXANE, D-

Common Name

English

DEXRAZOXANE [MART.]

Common Name

English

DEXRAZOXANE [HSDB]

Common Name

English

DEXRAZOXANE [JAN]

Common Name

English

ADR-529

Code

English

DEXRAZOXANE [VANDF]

Common Name

English

2,6-PIPERAZINEDIONE, 4,4'-(1-METHYL-1,2-ETHANEDIYL)BIS-, (S)-

Common Name

English

NSC-169780

Code

English

DEXRAZOXANE [EMA EPAR]

Common Name

English

ICRF-187

Code

English

RAZOXANE (+)-FORM [MI]

Common Name

English

(+)-(S)-4,4'-PROPYLENEDI-2,6-PIPERAZINEDIONE

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

V03AF02