Dexrazoxane (T3D2771)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2009-07-21 20:26:45 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2771
Identification
Common NameDexrazoxane
ClassSmall Molecule
DescriptionAn 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. 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.
Compound Type
  • Amide
  • Amine
  • Antineoplastic Agent
  • Cardiovascular Agent
  • Chelating Agent
  • Drug
  • Food Toxin
  • Immunosuppressive Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(+)-(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
Ao Nuo Xian
Cardioxane
Desrazoxane
Dexrazoxan
Dexrazoxano
Dexrazoxanum
Dextrorazoxane
Icrf-187
Savene
Totect
Zinecard
Chemical FormulaC11H16N4O4
Average Molecular Mass268.269 g/mol
Monoisotopic Mass268.117 g/mol
CAS Registry Number24584-09-6
IUPAC Name4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
Traditional Namedexrazoxane
SMILES[H][C@](C)(CN1CC(O)=NC(=O)C1)N1CC(O)=NC(=O)C1
InChI IdentifierInChI=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
InChI KeyInChIKey=BMKDZUISNHGIBY-ZETCQYMHSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acids and derivatives
Alternative Parents
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
  • Organoheterocyclic compound
  • Azacycle
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point191-197°C
Boiling PointNot Available
SolubilitySparingly soluble
LogP-2.6
Predicted Properties
PropertyValueSource
Water Solubility10.4 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.25 m³·mol⁻¹ChemAxon
Polarizability26.12 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0m2c-4910000000-46d13032d5f2c6472d9b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0490000000-80b0b21a495d2cc911a42016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1910000000-5a4bec9ae0f631c4c3282016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052b-8900000000-da472776fdfa9ff649dd2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-3ed9d12564a96e4f79a22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9010000000-913da0d82e09de14ca702016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-1b65fef6f408f48c6b592016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0910000000-8bbf646c07221a874c7c2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0aor-3790000000-825583366aa2049c64872021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0abc-9610000000-e2da7526d67ac758a8362021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-bd2978e4c0725b5d29bd2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05p6-5890000000-a1cb5b2cd96d828fbdaa2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9400000000-50d8c9f710f08bb206772021-09-22View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-16View Spectrum
Toxicity Profile
Route of ExposureIV administration results in complete bioavailability.
Mechanism of ToxicityThe 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.
MetabolismDexrazoxane 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
Toxicity ValuesIntraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsIntraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.
TreatmentThere is no known antidote for dexrazoxane. Instances of suspected overdose should be managed with good supportive care until resolution of myelosuppression and related conditions is complete. Management of overdose should include treatment of infections, fluid regulation, and maintenance of nutritional requirements. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00380
HMDB IDHMDB14524
PubChem Compound ID71384
ChEMBL IDCHEMBL1738
ChemSpider ID64479
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID50223
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDexrazoxane
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDexrazoxane
References
Synthesis ReferenceNot Available
MSDSLink
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. [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. [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. [17115008 ]
  4. Weiss G, Loyevsky M, Gordeuk VR: Dexrazoxane (ICRF-187). Gen Pharmacol. 1999 Jan;32(1):155-8. [9888268 ]
  5. Langer SW: Dexrazoxane for anthracycline extravasation. Expert Rev Anticancer Ther. 2007 Aug;7(8):1081-8. [18028016 ]
  6. Drugs.com [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. DNA topoisomerase 2-alpha
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 segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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. [10194547 ]
  3. 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. [11179439 ]
  4. 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. [11332155 ]
  5. 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. [11984069 ]
  6. 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. [12911317 ]
Target Details
2. DNA topoisomerase 2-beta
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
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. [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. [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. [10592235 ]