EPIRUBICIN HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H29NO11.ClH
Molecular Weight	579.98
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]1(C[C@H](N)[C@@H](O)[C@H](C)O1)O[C@H]2C[C@@](O)(CC3=C(O)C4=C(C(=O)C5=C(OC)C=CC=C5C4=O)C(O)=C23)C(=O)CO

InChI

InChIKey=MWWSFMDVAYGXBV-FGBSZODSSA-N

InChI=1S/C27H29NO11.ClH/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;1H/t10-,13-,15-,17-,22-,27-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C27H29NO11
Molecular Weight	543.5193
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/50778lbl.pdf |

Epirubicin is an anthracycline cytotoxic agent, is a 4'-epi-isomer of doxorubicin. The compound is marketed by Pfizer under the trade name Ellence in the US. It is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer. Although it is known that anthracyclines can interfere with a number of biochemical and biological functions within eukaryotic cells, the precise mechanisms of epirubicin’s cytotoxic and/or antiproliferative properties have not been completely elucidated. It is known, that epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis. Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/50778lbl.pdf	Crosslinking Agent 81

Conditions

Condition	Modality	Targets	Highest Phase	Product
Primary breast cancer 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/50778lbl.pdf	Primary		Approved 8429	ELLENCE Approved Use Epirubicin Hydrochloride Injection is indicated as a component of adjuvant therapy in patients with evidence of axillary node tumor involvement following resection of primary breast cancer Launch Date 1999

C_max

Value	Dose	Co-administered	Analyte	Population
5.7 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9.3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.2 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
35.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
31.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	150 mg/m² single, intravenous dose: 150 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
23% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/050807lbl.pdf	60 mg/m² single, intravenous dose: 60 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		EPIRUBICIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 200 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 200 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/10394119 Page: p.13,14	unhealthy, 31–62 n = 3 Health Status: unhealthy Condition: Ovarian carcinoma Age Group: 31–62 Sex: F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10394119 Page: p.13,14	DLT: Thrombocytopenia, Leukopenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 67%) Leukopenia (grade 4, 67%) Myelosuppression (grade 4, 100%) Stomatitis (grade 3, 33%) Sources: https://pubmed.ncbi.nlm.nih.gov/10394119 Page: p.13,14
95 mg/m2 1 times / day multiple, intravenous Overdose Dose: 95 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 95 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11	unhealthy, 36 n = 1 Health Status: unhealthy Condition: non-Hodgkin’s lymphoma Age Group: 36 Sex: M Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11	Disc. AE: Aplasia bone marrow, Mucositis... AEs leading to discontinuation/dose reduction: Aplasia bone marrow Mucositis (grade 4) Gastrointestinal bleeding Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11
320 mg/m2 single, intravenous Overdose Dose: 320 mg/m2 Route: intravenous Route: single Dose: 320 mg/m2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11	unhealthy, 63 n = 1 Health Status: unhealthy Condition: Breast cancer and liver metastasis Age Group: 63 Sex: F Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11	Disc. AE: Hyperthermia, Multiple organ failure... AEs leading to discontinuation/dose reduction: Hyperthermia Multiple organ failure Lactic acidosis Lactate dehydrogenase increased Anuria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.11
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1	Disc. AE: Soft tissue necrosis... AEs leading to discontinuation/dose reduction: Soft tissue necrosis (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1
120 mg/m2 1 times / 3 weeks multiple, intravenous Recommended Dose: 120 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 120 mg/m2, 1 times / 3 weeks Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Axillary node tumor involvement following resection of primary breast cancer Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1	DLT: Leukopenia, Neutropenia... Disc. AE: Toxic myocarditis, Congestive heart failure... Dose limiting toxicities: Leukopenia Neutropenia AEs leading to discontinuation/dose reduction: Toxic myocarditis (severe) Congestive heart failure (grade 3-5) Acute promyelocytic leukemia Myelosuppression (severe) Hyperuricemia Thrombophlebitis Thromboembolic event Pulmonary embolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/050778s021lbl.pdf Page: p.1

AEs

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00I9ZQ	https://www.aablocks.com/goods/Goods/detail?id=AA00I9ZQ
Achemtek	0104-013942	http://www.achemtek.com/56420-45-2
Acorn PharmaTech	ACN-038342	http://www.acornpharmatech.com/
Adooq BioScience	A12409	https://www.adooq.com/epirubicin.html
Alsachim	4680	http://www.alsachim.com/product-C6028-glo.bal-view.html
Ambinter	Amb21856008	http://www.ambinter.com/reference/21856008
Angene	AGN-PC-0WHA6U	http://www.angenechemical.com/productshow/AGN-PC-0WHA6U.html
AvaChem Scientific	2020B	http://www.avachem.com/productSearch.asp?2020B
Chem Scene	CS-2824	http://www.chemscene.com/56420-45-2.html
ChemMol	49424940	http://www.chemmol.com/chemmol/49424940.html
Lab Network	LN01341812	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341812
MedChem Express	HY-13624	https://www.medchemexpress.com/epirubicin.html
MuseChem	I004109	https://www.musechem.com/product/I004109.html
Parchem	28852	http://www.parchem.com/chemical-supplier-distributor/Epirubicin-018852.aspx
Smolecule	S527283	http://www.smolecule.com/products/s527283
THE BioTek	bt-267488	https://www.thebiotek.com/product/inhibitors/bt-267488
THE BioTek	bt-288837	https://www.thebiotek.com/product/others/bt-288837
Vesino Industrial Co Ltd	VA10821	http://www.vsnchem.com/goto/product/23243/
eNovation Chemicals	D681979	https://www.enovationchem.com/ProductDetails.asp?ProductID=D681979
iChemical	EBD2199801	http://www.ichemical.com/products/56420-45-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Docetaxel and epirubicin in advanced breast cancer.	2001	11346679
Adjuvant chemotherapy with high-dose cyclophosphamide, etoposide and cisplatin intensification without progenitor cell support in breast cancer patients with ten or more involved nodes: 5-year results of a pilot trial.	2001	11340373
Dose-dense sequential adjuvant chemotherapy with epirubicin, paclitaxel and CMF in high-risk breast cancer.	2001	11340372
Intensive cyclic chemotherapy with unprocessed whole blood support in advanced breast cancer.	2001	11327535
Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond.	2001	11306725
Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: results of two phase I studies.	2001	11244325
Comparison of double and triple high-dose chemotherapy with autologous blood stem cell transplantation in patients with metastatic breast cancer.	2001	11239170
Tolerability of the cytoprotective agent amifostine in elderly patients receiving chemotherapy: a comparative study.	2001 Apr	11335791
Carboplatin alone vs carboplatin plus epidoxorubicin as second-line therapy for cisplatin- or carboplatin-sensitive ovarian cancer.	2001 Apr	11277642
Primary high-grade mucosa-associated lymphoid tissue-type lymphoma of the cervix presenting as a common endocervical polyp.	2001 Apr	11260632
Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease.	2001 Apr 1	11286840
Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience.	2001 Apr 1	11286826
Expression and prognostic significance of catalase in malignant mesothelioma.	2001 Apr 1	11283936
Ondansetron plus metopimazine compared with ondansetron plus metopimazine plus prednisolone as antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy.	2001 Apr 1	11283143
Differential anthracycline sensitivity in two related human colon carcinoma cell lines expressing similar levels of P-glycoprotein.	2001 Apr 10	11248426
Dose-dense sequential chemotherapy with epirubicin and paclitaxel versus the combination, as first-line chemotherapy, in advanced breast cancer: a randomized study conducted by the Hellenic Cooperative Oncology Group.	2001 Apr 15	11304776
Clinical and pharmacologic study of the epirubicin and paclitaxel combination in women with metastatic breast cancer.	2001 Apr 15	11304775
Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up.	2001 Apr 6	11286464
Preoperative high-dose chemotherapy with peripheral blood stem cell support as a primary management of locally advanced breast cancer.	2001 Feb	11277186
[Advanced breast cancer with multiple bone metastases successfully treated with combined chemoendocrine-therapy of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) and 5'-DFUR (5'-deoxy-5-fluorouridine) + MPA (medroxyprogesterone acetate)--a case report].	2001 Feb	11242649
A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer.	2001 Feb	11207039
Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP-BLEO regimens.	2001 Feb	11168516
Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1).	2001 Feb	11167651
Thymidine kinase and thymidylate synthase in advanced breast cancer: response to tamoxifen and chemotherapy.	2001 Feb 15	11245445
Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.	2001 Feb 15	11181656
Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study.	2001 Feb 21	11181777
High-dose thiotepa and melphalan with hemopoietic progenitor support following induction therapy with epirubicin-paclitaxel-containing regimens in metastatic breast cancer (MBC).	2001 Jan	11249051
[Usefulness of ambulatory adjuvant chemotherapy with low-dose epirubicin in patients with axially-node positive breast cancer: Chiba Epirubicin Cooperative Study Group].	2001 Jan	11201379
Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells.	2001 Jan	11172689
Treatment of classical type Kaposi's sarcoma with paclitaxel.	2001 Jan-Feb	11299806
Synchronous gastric adenocarcinoma and MALT lymphoma in a patient with H. pylori infection. Could the two neoplasms share a common pathogenesis?	2001 Jan-Feb	11268940
Activation of caspase-3 in renal cell carcinoma cells by anthracyclines or 5-fluorouracil.	2001 Jul	11408917
Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting.	2001 Jun	11410493
Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.	2001 Jun	11378344
Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer.	2001 Jun 15	11408507
Metastatic eccrine porocarcinoma: response to docetaxel (Taxotere) chemotherapy.	2001 Mar	11332156
High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.	2001 Mar	11332148
Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.	2001 Mar	11320903
A phase II study of dose-intense ifosfamide plus epirubicin with hematopoietic growth factors for the treatment of patients with advanced soft tissue sarcomas; a novel sequential schedule.	2001 Mar	11320663
[Long-term survival of a patient with postoperative liver metastasis of stage IVa gallbladder cancer responding to hepatic arterial infusion chemotherapy].	2001 Mar	11265412
Efficacy of vinorelbine, epirubicin and prednisone combination regimen in pretreated elderly patients with aggressive non-Hodgkin's lymphoma.	2001 Mar	11255276
Contrast-enhanced subtraction harmonic sonography for evaluating treatment response in patients with hepatocellular carcinoma.	2001 Mar	11222201
Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2.	2001 Mar 15	11248153
Randomized trials of high dose chemotherapy for breast cancer.	2001 Mar 21	11250065
Docetaxel and epirubicin plus G-CSF as mobilizing treatment to support high-dose chemotherapy in breast cancer.	2001 Mar-Apr	11396215
Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study.	2001 May	11410417
Body surface area as a determinant of pharmacokinetics and drug dosing.	2001 May	11392451
Epirubicin glucuronidation is catalyzed by human UDP-glucuronosyltransferase 2B7.	2001 May	11302935
Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.	2001 May 15	11352968
Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma.	2001 May 15	11352960

Patents

Sample Use Guides

In Vivo Use Guide

Injection is administered to patients by intravenous infusion. Drug is given in 14 repeated 3- to 4-week cycles. The total dose may be given on Day 1 of each cycle 15 or divided equally and given on Days 1 and 8 of each cycle. The recommended starting dose is 100 to 120 mg/m2.

Route of Administration: Intravenous

In Vitro Use Guide

It was investigated the effect of combined treatment with the anthracycline agent epirubicin (EPI) and NK cells on human breast cancer cells. NK cells were obtained by autologous adoptive cell transfer from breast cancer patients and amplified for 14 days in vitro. The cytotoxicity of NK cells against breast cancer cells was higher following EPI (5.0 μg/ml) pretreatment than without EPI pretreatment or application of EPI alone. The expression of NKG2D ligands [unique long 16-binding protein (ULBP) 1, ULBP2, and major histocompatibility complex class I-related chain A] in breast cancer cells was upregulated by pretreatment with EPI, which also increased the secretion of interferon-γ and tumor necrosis factor-α and expression of perforin and granzyme B in NK cells. These results indicate that EPI-NK cell treatment has synergistic cytotoxic effects against breast cancer cells, and suggest that anthracycline-based chemotherapy and NK cell-based immunotherapy can be combined for more effective breast cancer treatment.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:32:04 GMT 2023` Edited by `admin` on `Fri Dec 15 15:32:04 GMT 2023`
Record UNII	22966TX7J5
Record Status	`Validated (UNII)`
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Name

Type

Language

EPIRUBICIN HYDROCHLORIDE

Official Name

English

EPIRUBICIN HYDROCHLORIDE [MI]

Common Name

English

EPIRUBICIN HCL [VANDF]

Common Name

English

ELLENCE

Brand Name

English

FARMORUBICINA

Brand Name

English

(1S,3S)-3-GLYCOLOYL-1,2,3,4,6,11-HEXAHYDRO-3,5,12-TRIHYDROXY-10-METHOXY-6,11-DIOXO-1-NAPHTHACENYL 3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-ARABINO-HEXOPYRANOSIDE HYDROCHLORIDE

Common Name

English

Epirubicin hydrochloride [WHO-DD]

Common Name

English

WP-697

Code

English

EPIRUBICIN HCL

Common Name

English

EPIRUBICIN HYDROCHLORIDE [JAN]

Common Name

English

EPIRUBICIN HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

EPIRUBICIN HYDROCHLORIDE [MART.]

Common Name

English

EPIRUBICIN HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

5,12-NAPHTHACENEDIONE, 10-((3-AMINO-2,3,6-TRIDEOXY-.ALPHA.-L-ARABINO-HEXOPYRANOSYL)OXY)-7,8,9,10-TETRAHYDRO-6,8,11-TRIHYDROXY-8-(HYDROXYACETYL)-1-METHOXY-, HYDROCHLORIDE, (8S-CIS)-

Common Name

English

IMI-28

Code

English

EPIRUBICIN HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

EPIRUBICIN HYDROCHLORIDE [USAN]

Common Name

English

EPIRUBICIN HYDROCHLORIDE [USP-RS]

Common Name

English

NSC-759195

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1594