T3DB: Epirubicin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:54 UTC

Update Date

2014-12-24 20:25:51 UTC

Accession Number

T3D2791

Identification

Common Name

Epirubicin

Class

Small Molecule

Description

Epirubicin 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

MOL SDF PDB SMILES InChI

Synonyms

Synonym
4'-Epiadriamycin
Ellence
Epiadriamycin
Epirubicin Ebewe
Epirubicina
Epirubicine
Epirubicinum
Pharmorubicin
Pidorubicina
Pidorubicine
Pidorubicinum

Chemical Formula

C₂₇H₂₉NO₁₁

Average Molecular Mass

543.519 g/mol

Monoisotopic Mass

543.174 g/mol

CAS Registry Number

56420-45-2

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 Name

epirubicin

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 Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Phenylpropanoids and polyketides

Class

Anthracyclines

Sub Class

Not Available

Direct Parent

Anthracyclines

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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

quinone (CHEBI:47898 )
monosaccharide derivative (CHEBI:47898 )
anthracycline antibiotic (CHEBI:47898 )
aminoglycoside (CHEBI:47898 )
deoxy hexoside (CHEBI:47898 )
anthracycline (CHEBI:47898 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Caveolae
Cell surface
Cytoplasm
Cytosol
Extracellular
Membrane
Membrane Fraction
Microsome
Microtubule
Mitochondrion
Nuclear Membrane
Plasma Membrane
Sarcoplasmic Reticulum
Soluble Fraction

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Apoptosis	Not Available	map04210
Cell cycle	Not Available	map04110
Abc transporters	Not Available	map02010
Endocytosis	Not Available	map04144
Ubiquitin mediated proteolysis	Not Available	map04120
Homologous recombination	Not Available	map03440
Glutathione Metabolism	SMP00015	map00480
Dna replication	Not Available	map03030

Applications

Biological Roles

Chemical Roles

EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	344.53°C
Boiling Point	Not Available
Solubility	0.093 mg/ml
LogP	-0.5

Predicted Properties

Property	Value	Source
Water Solubility	1.18 g/L	ALOGPS
logP	1.41	ALOGPS
logP	0.92	ChemAxon
logS	-2.7	ALOGPS
pKa (Strongest Acidic)	9.53	ChemAxon
pKa (Strongest Basic)	8.94	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	6	ChemAxon
Polar Surface Area	206.07 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	134.59 m³·mol⁻¹	ChemAxon
Polarizability	53.88 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9100210000-2b807cbc2c92b3239ce2	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0ff0-9800335000-532e07e6705247206510	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_6) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_7) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_5) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_6) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_7) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_8) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_9) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_10) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_11) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_12) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_13) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_14) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_15) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_16) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_2_17) - 70eV, Positive	Not Available	2021-10-13	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0002-0309010000-24e2012ac5fb139c1f97	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0002-0309010000-24e2012ac5fb139c1f97	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-03ka-1209000000-c2af8c9285b9bdd05415	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-002b-0009000000-f5988cefa7b2daf5f151	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00ov-0005390000-f948ee4b89881c04094f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00l2-1319310000-6809908c73812c7294b0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0pea-4109100000-aa6428ee7c0e41ed2d97	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-01ox-0002390000-1d86ac1de2afc3f4ce0d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-08fv-5209740000-2da58c964c8e55c74f5e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-08fr-7207900000-9dd3041a50cddfad58dc	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000t-0009000000-c2261d7295031ec8b1a3	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00kr-0009000000-c0d23b7b41211d5bcf7d	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-1009230000-adab49e4224b716b7c2f	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004j-0409070000-1f754ac056625a678f5e	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01u1-2619140000-93871ebd236804cb7e03	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03e9-4910200000-64c8902380be8a1fd183	2021-09-24	View Spectrum

Toxicity Profile

Route of Exposure

Intravenous

Mechanism of Toxicity

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.

Metabolism

Extensively 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For use as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

bone marrow aplasia, grade 4 mucositis, and gastrointestinal bleeding

Treatment

If 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

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

47898

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Epirubicin

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Epirubicin

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.

MSDS

T3D2791.pdf

General References

Pharmacia. Ellence® (epirubicin hydrochloride injection) full prescribing information. New York, NY; 2007 Feb.
Pharmacia. EllenceÃ‚Â® (epirubicin hydrochloride injection) full prescribing information. New York, NY; 2007 Feb.
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Not 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

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 ]
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 ]
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 ]

Target Details

2. 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

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 ]
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 ]
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 ]

Target Details

3. Chromodomain-helicase-DNA-binding protein 1

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

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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 ]

Epirubicin (T3D2791)

Structure for T3D2791: Epirubicin

Targets

References

References

References