56390-09-1

Basic information

• Product Name: Epirubicin hydrochloride
• Synonyms: (8s-cis)-rochlorid;4’-epi-adriamycinhydrochloride;5,12-naphthacenedione,10-((3-amino-2,3,6-trideoxy-alpha-l-arabino-hexopyranosy;8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-l)oxy)-hyd;EPIRUBICIN HYDROCHLORIDE EP STANDARD;EpirubicinHc,LEp5,;Adrial;Ellence, Farmorubicin, Pharmorubicin
• CAS NO: 56390-09-1
• Molecular Formula: C27H30ClNO11
• Molecular Weight: 579.9802
• EINECS: 260-145-2
• Product Categories: Antibiotics;Intermediates & Fine Chemicals;Pharmaceuticals;API;Antineoplastic;Anti-cancer&immunity
• Mol File: 56390-09-1.mol
• Article Data: 0

Chemical Properties

• Melting Point: 185°C dec.
• Boiling Point: 810.3 °C at 760 mmHg
• Flash Point: 443.8℃
• Appearance: red to deep red/
• Density: 1.61 g/cm³
• Vapor Pressure: 9.64E-28mmHg at 25°C
• Refractive Index: 1.709
• Storage Temp.: Desiccate at +4°C
• Solubility: Soluble in DMSO to 100mM, or in ethanol to 10mM
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 3 months.
• CAS DataBase Reference: Epirubicin hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Epirubicin hydrochloride(56390-09-1)
• EPA Substance Registry System: Epirubicin hydrochloride(56390-09-1)

Safety Data

• Hazard Codes: Xn
• Statements: 22-63-62-46-40
• Safety Statements: 36/37/38-45-46
• WGK Germany: 3
• RTECS: QI9295750
• Hazardous Substances Data: 56390-09-1(Hazardous Substances Data)

Usage

Description

Epirubicin hydrochloride is an antitumor antibiotic that is a stereoisomer of doxorubicin, differing at the 4'-position of the amino sugar moiety. It is an orange-red crystalline solid with the brand names Ellence (Pfizer) and FARMORUBICIN. Epirubicin hydrochloride has demonstrated utility in the treatment of various types of cancer, including mammary, gastric, colorectal, pulmonary, and ovarian carcinomas, as well as malignant lymphoma, melanoma, and soft tissue sarcoma. It is reported to be less cardiotoxic than doxorubicin.

Uses

Used in Oncology:
Epirubicin hydrochloride is used as a cell-permeable anthracycline anti-tumor antibiotic for the treatment of various cancers. It has shown high rates of complete or partial remission when used either alone or in combination therapies. The application reason is its cytotoxic effect on cancer cells, which is comparable to that of doxorubicin (ID50s = 9 μM for HeLa cells).
Epirubicin hydrochloride is used as an anticancer agent for the following cancers:
Mammary carcinoma
Gastric carcinoma
Colorectal carcinoma
Pulmonary carcinoma
Ovarian carcinoma
Malignant lymphoma
Melanoma
Soft tissue sarcoma
The application reason for its use in these cancers is its ability to partially detoxify dose-limiting side effects through β-glucuronidation, making it a less cardiotoxic alternative to doxorubicin. Additionally, epirubicin hydrochloride has demonstrated synergistic anticancer effects when combined with conventional chemotherapeutic drugs, enhancing chemo-sensitivity and efficacy in resistant cases.

Originator

Erbamont (Italy)

Biological Functions

This stereoisomer of doxorubicin has the 4′-hydroxy group of the daunosamine sugar oriented in the β-position . Epirubicin will be slowly reduced to the active C13 alcohol (epirubicinol), giving it a 30- to 38-hour half life, which is similar to that of doxorubicin. Unlike doxorubicinol, however, which was equally active with doxorubicin, epirubicinol has only one-tenth the activity of its parent drug and is not believed to contribute significantly to the therapeutic action of this agent.

Biological Activity

Antibiotic antitumor agent. Inhibits the synthesis and function of DNA (IC 50 = 62.7 μ M in rat glioblastoma cell lines) and inhibits the relaxing property of topoisomerase II.

Clinical Use

Epirubicin is indicated for use in breast cancer, and the starting dose is 100 to 120 mg/m2 (compared to a starting dose of 60–75 mg/m2 for doxorubicin).

Side effects

The side effects and precautions are as outlined previously for doxorubicin, although there is a lower risk of serious myocardial toxicity or myelotoxicity.

Drug interactions

Potentially hazardous interactions with other drugsAntipsychotics: avoid with clozapine - increased risk of agranulocytosis.Ciclosporin: increased risk of neurotoxicityCytotoxics: possible increased risk of cardiotoxicity with trastuzumab - avoid for up to 28 weeks after stopping trastuzumab.Ulcer-healing drugs: concentration increased by cimetidine. Vaccines: avoid with live vaccines

Metabolism

Cleavage of the epimerized sugar will occur before excretion, generating an aglycone that is indistinguishable from that generated by doxorubicin. Although excretion is primarily biliary, dosage reduction in severe renal impairment, as well as in hepatic dysfunction, is warranted.

References

1) Cersosimo?et al. (1986),?Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue; J. Clin. Oncol.,?4?425 2) Spadari?et al. (1986),?DNA polymerases and DNA topoisomerases as targets for the development of anticancer drugs; Anticancer Res.,?6?935 3) Minotti?et al. (2004),?Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity; Pharmacol. Rev.,?56?185 4) Mercuro?et al. (2007),?Early epirubicin-induced myocardial dysfunction revealed by serial tissue Doppler echocardiography: correlation with inflammatory and oxidative stress markers; Oncologist,?12?1124

InChI:InChI=1/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