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Record Information
Version2.0
Creation Date2009-07-21 20:26:54 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2791
Identification
Common NameEpirubicin
ClassSmall Molecule
DescriptionEpirubicin is only found in individuals that have used or taken this drug. It is an anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA. Epirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
Compound Type
  • Amine
  • Antibiotic, Antineoplastic
  • Antineoplastic Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
4'-Epiadriamycin
Ellence
Epiadriamycin
Epirubicin Ebewe
Epirubicina
Epirubicine
Epirubicinum
Pharmorubicin
Pidorubicina
Pidorubicine
Pidorubicinum
Chemical FormulaC27H29NO11
Average Molecular Mass543.519 g/mol
Monoisotopic Mass543.174 g/mol
CAS Registry Number56420-45-2
IUPAC Name(8S,10S)-10-{[(2R,4S,5R,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione
Traditional Nameepirubicin
SMILES[H][C@]1(N)C[C@]([H])(O[C@@]2([H])C[C@@](O)(CC3=C(O)C4=C(C(O)=C23)C(=O)C2=C(C=CC=C2OC)C4=O)C(=O)CO)O[C@@]([H])(C)[C@]1([H])O
InChI IdentifierInChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22-,27-/m0/s1
InChI KeyInChIKey=AOJJSUZBOXZQNB-VTZDEGQISA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as anthracyclines. These are polyketides containing a tetracenequinone ring structure with a sugar attached by glycosidic linkage.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassAnthracyclines
Sub ClassNot Available
Direct ParentAnthracyclines
Alternative Parents
Substituents
  • Anthracycline
  • Anthracyclinone-skeleton
  • Aminoglycoside core
  • Tetracenequinone
  • 9,10-anthraquinone
  • 1,4-anthraquinone
  • Anthracene
  • Hexose monosaccharide
  • Glycosyl compound
  • O-glycosyl compound
  • Tetralin
  • Aryl ketone
  • Anisole
  • Amino saccharide
  • Alkyl aryl ether
  • Benzenoid
  • Oxane
  • Monosaccharide
  • Vinylogous acid
  • Tertiary alcohol
  • Alpha-hydroxy ketone
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Ketone
  • Acetal
  • Organoheterocyclic compound
  • Polyol
  • Ether
  • Oxacycle
  • Alcohol
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Amine
  • Primary amine
  • Primary alcohol
  • Primary aliphatic amine
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Caveolae
  • Cell surface
  • Cytoplasm
  • Cytosol
  • Extracellular
  • Membrane
  • Membrane Fraction
  • Microsome
  • Microtubule
  • Mitochondrion
  • Nuclear Membrane
  • Plasma Membrane
  • Sarcoplasmic Reticulum
  • Soluble Fraction
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
Abc transportersNot Availablemap02010
EndocytosisNot Availablemap04144
Ubiquitin mediated proteolysisNot Availablemap04120
Homologous recombinationNot Availablemap03440
Glutathione MetabolismSMP00015 map00480
Dna replicationNot Availablemap03030
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point344.53°C
Boiling PointNot Available
Solubility0.093 mg/ml
LogP-0.5
Predicted Properties
PropertyValueSource
Water Solubility1.18 g/LALOGPS
logP1.41ALOGPS
logP0.92ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)9.53ChemAxon
pKa (Strongest Basic)8.94ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area206.07 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity134.59 m³·mol⁻¹ChemAxon
Polarizability53.88 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9100210000-2b807cbc2c92b3239ce2JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-0ff0-9800335000-532e07e6705247206510JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_7) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_15) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_16) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_17) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0309010000-24e2012ac5fb139c1f97JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0309010000-24e2012ac5fb139c1f97JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-03ka-1209000000-c2af8c9285b9bdd05415JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-002b-0009000000-f5988cefa7b2daf5f151JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00ov-0005390000-f948ee4b89881c04094fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00l2-1319310000-6809908c73812c7294b0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0pea-4109100000-aa6428ee7c0e41ed2d97JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01ox-0002390000-1d86ac1de2afc3f4ce0dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-08fv-5209740000-2da58c964c8e55c74f5eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-08fr-7207900000-9dd3041a50cddfad58dcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000t-0009000000-c2261d7295031ec8b1a3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-0009000000-c0d23b7b41211d5bcf7dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-1009230000-adab49e4224b716b7c2fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004j-0409070000-1f754ac056625a678f5eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01u1-2619140000-93871ebd236804cb7e03JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03e9-4910200000-64c8902380be8a1fd183JSpectraViewer
Toxicity Profile
Route of ExposureIntravenous
Mechanism of ToxicityEpirubicin has antimitotic and cytotoxic activity. It inhibits nucleic acid (DNA and RNA) and protein synthesis through a number of proposed mechanisms of action: Epirubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. It also interferes with DNA replication and transcription by inhibiting DNA helicase activity.
MetabolismExtensively and rapidly metabolized in the liver. Epirubicin is also metabolized by other organs and cells, including red blood cells. The four main metabolic routes are: (1) reduction of the C-13 keto-group with the formation of the 13(S)-dihydro derivative, epirubicinol; (2) conjugation of both the unchanged drug and epirubicinol with glucuronic acid; (3) loss of the amino sugar moiety through a hydrolytic process with the formation of the doxorubicin and doxorubicinol aglycones; and (4) loss of the amino sugar moiety through a redox process with the formation of the 7-deoxy-doxorubicin aglycone and 7-deoxy-doxorubicinol aglycone. Epirubicinol exhibits in vitro cytoxic activity (~10% that of epirubicin), but it is unlikely to reach sufficient concentrations in vivo to produce cytotoxic effects. Route of Elimination: Epirubicin and its major metabolites are eliminated through biliary excretion and, to a lesser extent, by urinary excretion. Half Life: Half-lives for the alpha, beta, and gamma phases of about 3 minutes, 2.5 hours and 33 hours, respectively
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.
Minimum Risk LevelNot Available
Health EffectsNot Available
Symptomsbone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding
TreatmentIf an overdose occurs, supportive treatment (including antibiotic therapy, blood and platelet transfusions, colony-stimulating factors, and intensive care as needed) should be provided until the recovery of toxicities. Delayed CHF has been observed months after anthracycline administration. Patients must be observed carefully over time for signs of CHF and provided with appropriate supportive therapy. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00445
HMDB IDHMDB14588
PubChem Compound ID41867
ChEMBL IDCHEMBL1237042
ChemSpider ID38201
KEGG IDC11230
UniProt IDNot Available
OMIM ID
ChEBI ID47898
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEpirubicin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEpirubicin
References
Synthesis Reference

Marcel van der Rijst, Johan Wilhelm Scheeren, Dick de Vos, “Process for preparing epirubicin or acid addition salts thereof from daunorubicin.” U.S. Patent US5874550, issued September, 1996.

MSDST3D2791.pdf
General References
  1. Pharmacia. Ellence® (epirubicin hydrochloride injection) full prescribing information. New York, NY; 2007 Feb.
  2. Pharmacia. Ellence® (epirubicin hydrochloride injection) full prescribing information. New York, NY; 2007 Feb.
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Ganzina F: 4'-epi-doxorubicin, a new analogue of doxorubicin: a preliminary overview of preclinical and clinical data. Cancer Treat Rev. 1983 Mar;10(1):1-22. [6342772 ]
  2. Williams LD, Frederick CA, Ughetto G, Rich A: Ternary interactions of spermine with DNA: 4'-epiadriamycin and other DNA: anthracycline complexes. Nucleic Acids Res. 1990 Sep 25;18(18):5533-41. [2216725 ]
  3. Podell ER, Harrington DJ, Taatjes DJ, Koch TH: Crystal structure of epidoxorubicin-formaldehyde virtual crosslink of DNA and evidence for its formation in human breast-cancer cells. Acta Crystallogr D Biol Crystallogr. 1999 Sep;55(Pt 9):1516-23. [10489446 ]
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. Petit T, Wilt M, Velten M, Millon R, Rodier JF, Borel C, Mors R, Haegele P, Eber M, Ghnassia JP: Comparative value of tumour grade, hormonal receptors, Ki-67, HER-2 and topoisomerase II alpha status as predictive markers in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Eur J Cancer. 2004 Jan;40(2):205-11. [14728934 ]
  2. Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdottir K, Olsen KE, Mouridsen H, Ejlertsen B: retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol. 2005 Oct 20;23(30):7483-90. [16234514 ]
  3. Liang CH, Shiu LY, Chang LC, Sheu HM, Kuo KW: Solamargine upregulation of Fas, downregulation of HER2, and enhancement of cytotoxicity using epirubicin in NSCLC cells. Mol Nutr Food Res. 2007 Aug;51(8):999-1005. [17639997 ]
General Function:
Methylated histone binding
Specific Function:
ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3. Required for maintaining open chromatin and pluripotency in embryonic stem cells.
Gene Name:
CHD1
Uniprot ID:
O14646
Molecular Weight:
196685.865 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 ]