Identification

Name
Dexrazoxane
Accession Number
DB00380  (APRD00090, DB02444)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

An antimitotic agent with immunosuppressive properties. Dexrazoxane, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem] The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.

Structure
Thumb
Synonyms
  • (+)-(S)-4,4'-Propylenedi-2,6-piperazinedione
  • (+)-1,2-Bis(3,5-dioxo-1-piperazinyl)propane
  • 4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
  • Dexrazoxan
  • Dexrazoxane
  • Dexrazoxano
  • Dexrazoxanum
  • Dextrorazoxane
External IDs
ADR 529 / ADR-529 / ICRF-187 / NSC 169780 / NSC-169780
Product Ingredients
IngredientUNIICASInChI Key
Dexrazoxane hydrochloride5346058Q7S149003-01-0BIFMNMPSIYHKDN-FJXQXJEOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SaveneInjection, solution, concentrate20 mg/mlIntravenousClinigen Healthcare Ltd.2006-07-28Not applicableEu
TotectInjection, powder, lyophilized, for solution500 mg/1IntravenousCumberland Pharmaceuticals2017-07-25Not applicableUs
ZinecardPowder, for solution250 mgIntravenousPfizer1995-12-31Not applicableCanada
ZinecardInjection, powder, lyophilized, for solution250 mg/25mLIntravenousPharmacia & Upjohn Inc1995-05-26Not applicableUs
ZinecardPowder, for solution500 mgIntravenousPfizer1995-12-31Not applicableCanada
ZinecardInjection, powder, lyophilized, for solution500 mg/50mLIntravenousPharmacia & Upjohn Inc1995-05-26Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DexrazoxaneInjection, solution500 mg/50mLIntravenousBreckenridge Pharmaceutical, Inc.2016-12-05Not applicableUs
DexrazoxaneInjection, powder, lyophilized, for solution500 mg/50mLIntravenousAlvogen, Inc.2017-09-01Not applicableUs
DexrazoxaneInjection, powder, lyophilized, for solution500 mg/50mLIntravenousGland Pharma Limited2016-12-05Not applicableUs
Dexrazoxane HydrochlorideKitMylan Institutional2011-11-18Not applicableUs
Dexrazoxane HydrochlorideKitMylan Institutional2011-11-18Not applicableUs
International/Other Brands
Ao Nuo Xian (AosaiKang Pharmaceutical) / Cardioxane (Novartis) / Dexrazoxane (Raffo) / Savene (TopoTarget) / Totect (TopoTarget)
Categories
UNII
048L81261F
CAS number
24584-09-6
Weight
Average: 268.2691
Monoisotopic: 268.11715502
Chemical Formula
C11H16N4O4
InChI Key
BMKDZUISNHGIBY-ZETCQYMHSA-N
InChI
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
IUPAC Name
4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
SMILES
C[[email protected]@H](CN1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1

Pharmacology

Indication

For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.

Structured Indications
Pharmacodynamics

Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin 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. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.

Mechanism of action

The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.

TargetActionsOrganism
ADNA topoisomerase 2-alpha
inhibitor
Human
UDNA topoisomerase 2-betaNot AvailableHuman
Absorption

IV administration results in complete bioavailability.

Volume of distribution
  • 9 to 22.6 L/m^2
Protein binding

Very low (< 2%)

Metabolism

Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions.

Route of elimination

Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine.

Half life

2.5 hours

Clearance
  • 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane]
  • 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane]
Toxicity

Intraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Dexrazoxane.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Dexrazoxane.Experimental
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Dexrazoxane.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Dexrazoxane.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Dexrazoxane.Approved
ClozapineThe risk or severity of adverse effects can be increased when Dexrazoxane is combined with Clozapine.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Dexrazoxane.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Dexrazoxane.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Dexrazoxane.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Dexrazoxane.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Dexrazoxane.Approved
Dimethyl sulfoxideThe therapeutic efficacy of Dexrazoxane can be decreased when used in combination with Dimethyl sulfoxide.Approved, Vet Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Dexrazoxane.Approved, Investigational
DoxorubicinThe therapeutic efficacy of Doxorubicin can be decreased when used in combination with Dexrazoxane.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Dexrazoxane.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Dexrazoxane.Experimental
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Dexrazoxane.Withdrawn
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Dexrazoxane.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Dexrazoxane.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Dexrazoxane.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Dexrazoxane.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Dexrazoxane.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Dexrazoxane.Experimental
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Dexrazoxane.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Hasinoff BB, Herman EH: Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140-4. [PubMed:17652819]
  2. Hasinoff BB: The use of dexrazoxane for the prevention of anthracycline extravasation injury. Expert Opin Investig Drugs. 2008 Feb;17(2):217-23. doi: 10.1517/13543784.17.2.217. [PubMed:18230055]
  3. Kik K, Szmigiero L: [Dexrazoxane (ICRF-187)--a cardioprotectant and modulator of action of some anticancer drugs]. Postepy Hig Med Dosw (Online). 2006;60:584-90. [PubMed:17115008]
  4. Weiss G, Loyevsky M, Gordeuk VR: Dexrazoxane (ICRF-187). Gen Pharmacol. 1999 Jan;32(1):155-8. [PubMed:9888268]
  5. Langer SW: Dexrazoxane for anthracycline extravasation. Expert Rev Anticancer Ther. 2007 Aug;7(8):1081-8. [PubMed:18028016]
External Links
Human Metabolome Database
HMDB14524
ChemSpider
64479
ChEBI
50223
ChEMBL
CHEMBL1738
Therapeutic Targets Database
DAP000649
PharmGKB
PA449259
HET
CDX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dexrazoxane
ATC Codes
V03AF02 — Dexrazoxane
AHFS Codes
  • 92:00.00 — Miscellaneous Therapeutic Agents
FDA label
Download (162 KB)
MSDS
Download (161 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1CompletedTreatmentCardiac Toxicity / Unspecified Childhood Solid Tumor, Protocol Specific1
1CompletedTreatmentSarcomas1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1RecruitingTreatmentRecurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Neuroblastoma / Unspecified Childhood Solid Tumor, Protocol Specific1
1TerminatedTreatmentAcute Leukemias of Ambiguous Lineage / Acute Undifferentiated Leukemia (AUL) / Angioimmunoblastic T-Cell Lymphoma / Blastic Phase Chronic Myelogenous Leukemia / Childhood Burkitt Lymphoma / Childhood Chronic Myelogenous Leukemia / Childhood Diffuse Large Cell Lymphoma / Childhood Immunoblastic Large Cell Lymphoma / Childhood Nasal Type Extranodal NK/T-cell Lymphoma / Cutaneous B-Cell Non-Hodgkin Lymphoma / Hepatosplenic T-Cell Lymphoma / Intraocular Lymphoma / Noncutaneous Extranodal Lymphoma / Peripheral T-Cell Lymphoma (PTCL) / Recurrent Childhood Acute Lymphoblastic Leukemia / Recurrent Childhood Acute Myeloid Leukemia / Recurrent Childhood Anaplastic Large Cell Lymphoma / Recurrent Childhood Grade III Lymphomatoid Granulomatosis / Recurrent Childhood Large Cell Lymphoma / Recurrent Childhood Lymphoblastic Lymphoma / Recurrent Childhood Small Noncleaved Cell Lymphoma / Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma / Recurrent Mycosis Fungoides/Sezary Syndrome / Recurrent/Refractory Childhood Hodgkin Lymphoma / Refractory Chronic Lymphocytic Leukemia / Refractory Hairy Cell Leukemia / Relapsing Chronic Myelogenous Leukemia / Small Intestine Lymphoma / Unspecified Childhood Solid Tumor, Protocol Specific1
1TerminatedTreatmentHeart Defects,Congenital1
1TerminatedTreatmentLung Cancer Metastatic / Sarcoma, Osteogenic1
1, 2Active Not RecruitingTreatmentRecurrent Childhood Acute Lymphoblastic Leukemia1
1, 2CompletedTreatmentExtravasations of Anthracycline Anti-cancer Agents1
1, 2Unknown StatusTreatmentSoft Tissue Sarcoma (STS)1
2Active Not RecruitingTreatmentSarcomas1
2CompletedTreatmentCentral Nervous System Tumor, Pediatric1
2CompletedTreatmentEwing's Sarcoma (ES) / Neuroblastomas / Rhabdomyosarcomas1
2CompletedTreatmentSarcomas1
2RecruitingTreatmentAntineoplastic Combined Chemotherapy Protocols1
2RecruitingTreatmentEpithelioid Sarcoma / Fibrosarcomas malignant / Hemangiosarcoma / Leiomyosarcomas / Liposarcoma / Malignant Peripheral Nerve Sheath Tumour (MPNST) / Myxofibrosarcoma / Soft Tissue Sarcoma (STS) / Synovial Sarcoma / Undifferentiated Pleomorphic Sarcoma1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndromes1
2RecruitingTreatmentRhabdomyosarcomas1
2TerminatedTreatmentCancer, Breast1
2TerminatedTreatmentCardiac Toxicity / Sarcomas1
2TerminatedTreatmentEwing's Sarcoma (ES)1
2TerminatedTreatmentSarcomas1
2Unknown StatusTreatmentDisseminated Sclerosis1
2, 3CompletedTreatmentAnthracycline Extravasation1
2, 3CompletedTreatmentDrug Extravasation1
3Active Not RecruitingTreatmentDrug/Agent Toxicity by Tissue/Organ / Leukemias1
3CompletedSupportive CareCardiac Toxicity / Leukemias / Malignant Lymphomas1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3CompletedTreatmentCardiac Toxicity / Malignant Lymphomas2
3CompletedTreatmentCardiac Toxicity / Sarcomas1
3Not Yet RecruitingTreatmentChildhood Ganglioneuroblastoma / Childhood Neuroblastoma / NMYC Gene Amplification / Recurrent Neuroblastoma1
3RecruitingTreatmentAcute Lymphoblastic Leukaemias (ALL) / B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 / BCR-ABL1 Fusion Protein Expression / Minimal Residual Disease / Philadelphia Chromosome Positive / T Acute Lymphoblastic Leukemia / Untreated Adult Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3TerminatedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3TerminatedTreatmentCardiac Toxicity / Inflammatory carcinoma of the breast / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IV Breast Cancer1
3WithdrawnTreatmentSarcomas1
Not AvailableCompletedSupportive CareNausea / Sarcomas / Vomiting1
Not AvailableTerminatedTreatmentSarcoma, Osteogenic1

Pharmacoeconomics

Manufacturers
  • Bedford laboratories div ben venue laboratories inc
  • Topotarget as
  • Pharmacia and upjohn co
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntravenous500 mg/50mL
Kit
Injection, solution, concentrateIntravenous20 mg/ml
Injection, powder, lyophilized, for solutionIntravenous500 mg/1
Injection, powder, lyophilized, for solutionIntravenous250 mg/25mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/50mL
Powder, for solutionIntravenous250 mg
Powder, for solutionIntravenous500 mg
Prices
Unit descriptionCostUnit
Zinecard 500 mg vial517.18USD vial
Dexrazoxane 500 mg vial492.55USD vial
Zinecard 250 mg vial258.59USD vial
Dexrazoxane 250 mg vial246.28USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5242901No1993-09-072010-09-07Us
US6727253No2000-03-132020-03-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)191-197 °CNot Available
water solubilitySparingly solubleNot Available
logP-2.6Not Available
pKa2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility10.4 mg/mLALOGPS
logP-1ALOGPS
logP-2.7ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)11.2ChemAxon
pKa (Strongest Basic)3.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area98.82 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.25 m3·mol-1ChemAxon
Polarizability26.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8518
Blood Brain Barrier+0.6387
Caco-2 permeable-0.6144
P-glycoprotein substrateSubstrate0.8766
P-glycoprotein inhibitor IInhibitor0.6576
P-glycoprotein inhibitor IINon-inhibitor0.9653
Renal organic cation transporterNon-inhibitor0.7348
CYP450 2C9 substrateNon-substrate0.8399
CYP450 2D6 substrateNon-substrate0.7872
CYP450 3A4 substrateSubstrate0.5139
CYP450 1A2 substrateNon-inhibitor0.9458
CYP450 2C9 inhibitorNon-inhibitor0.8828
CYP450 2D6 inhibitorNon-inhibitor0.9348
CYP450 2C19 inhibitorNon-inhibitor0.7777
CYP450 3A4 inhibitorNon-inhibitor0.9666
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9741
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9077
BiodegradationNot ready biodegradable0.991
Rat acute toxicity2.4267 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.941
hERG inhibition (predictor II)Non-inhibitor0.8929
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acids and derivatives
Alternative Parents
Dioxopiperazines / N-alkylpiperazines / N-unsubstituted carboxylic acid imides / Dicarboximides / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alpha-amino acid or derivatives / Dioxopiperazine / N-alkylpiperazine / 1,4-diazinane / Piperazine / Carboxylic acid imide / Dicarboximide / Carboxylic acid imide, n-unsubstituted / Tertiary aliphatic amine / Tertiary amine
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
razoxane (CHEBI:50223)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
Molecular Weight
174383.88 Da
References
  1. Hasinoff BB, Chee GL, Thampatty P, Allan WP, Yalowich JC: The cardioprotective and DNA topoisomerase II inhibitory agent dexrazoxane (ICRF-187) antagonizes camptothecin-mediated growth inhibition of Chinese hamster ovary cells by inhibition of DNA synthesis. Anticancer Drugs. 1999 Jan;10(1):47-54. [PubMed:10194547]
  2. Hasinoff BB, Abram ME, Barnabe N, Khelifa T, Allan WP, Yalowich JC: The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol. 2001 Mar;59(3):453-61. [PubMed:11179439]
  3. Langer SW, Sehested M, Jensen PB: Dexrazoxane is a potent and specific inhibitor of anthracycline induced subcutaneous lesions in mice. Ann Oncol. 2001 Mar;12(3):405-10. [PubMed:11332155]
  4. Hasinoff BB, Takeda K, Ferrans VJ, Yu ZX: The doxorubicin cardioprotective agent dexrazoxane (ICRF-187) induces endopolyploidy in rat neonatal myocytes through inhibition of DNA topoisomerase II. Anticancer Drugs. 2002 Mar;13(3):255-8. [PubMed:11984069]
  5. Renodon-Corniere A, Jensen LH, Nitiss JL, Jensen PB, Sehested M: Analysis of bisdioxopiperazine dexrazoxane binding to human DNA topoisomerase II alpha: decreased binding as a mechanism of drug resistance. Biochemistry. 2003 Aug 19;42(32):9749-54. [PubMed:12911317]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Hasinoff BB, Herman EH: Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol. 2007;7(2):140-4. [PubMed:17652819]
  8. Kik K, Szmigiero L: [Dexrazoxane (ICRF-187)--a cardioprotectant and modulator of action of some anticancer drugs]. Postepy Hig Med Dosw (Online). 2006;60:584-90. [PubMed:17115008]
  9. Hasinoff BB, Abram ME, Chee GL, Huebner E, Byard EH, Barnabe N, Ferrans VJ, Yu ZX, Yalowich JC: The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces endopolyploidy in Chinese hamster ovary cells. J Pharmacol Exp Ther. 2000 Nov;295(2):474-83. [PubMed:11046078]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein kinase c binding
Specific Function
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name
TOP2B
Uniprot ID
Q02880
Uniprot Name
DNA topoisomerase 2-beta
Molecular Weight
183265.825 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2017 09:35