K 912, NC 6300, Epirubicin nano

 Epirubicin

Cancer Research UK

 Epirubicin

Irish Cancer Society

 Epirubicin

Macmillan Cancer Support

 Epirubicin

NHS Evidence

 Epirubicin – Substance Summary

PubChem

 EpirubicinEmail

MedlinePlus

– See more at: http://www.cancerindex.org/Epirubicin#sthash.BBioCC6K.dpuf

PHASE 1 JAPAN SOLID TUMOURS

DNA/RNA Synthesis Inhibitor

WITH Nano Carrier Co.,Ltdhttp://pdf.irpocket.com/C4571/qnwX/eFou/vG1J.pdf

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CAS FREE FORM. 56420-45-2

Smiles

• O=C2c1c(O)c5c(c(O)c1C(=O)c3cccc(OC)c23)C[C@@](O)(C(=O)CO)C[C@@H]5O[C@@H]4O[C@H]([C@H](O)[C@@H](N)C4)C
• NMR
• http://file.selleckchem.com/downloads/nmr/S122302-Epirubicin-Hydrochloride-NMR-Selleck.pdf
• http://www.medkoo.com/Product-Data/Epirubicin/Epirubicin-QC-TZC20130604web.pdf

• Epirubicin
  CAS No.:	56420-45-2
  Synonyms:	4′-Epi-DX; Epirubicina; WP 697; Pidorubicin; 4′-epiadriamycin; Adriblastin; epi-dx; Epiadriamycin; farmorubicin; imi28; Farmarubicin;
  Formula:	C27H29NO11
  Exact Mass:	543.17400

NC-6300, an epirubicin-incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin.

Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin-incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC-6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid-labile hydrazone bond. The conjugate forms a micellar structure of 40-80 nm in diameter in an aqueous milieu. NC-6300 (10, 15 mg/kg) and epirubicin (10 mg/kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL/6 mice that were given NC-6300 (10 mg/kg) or epirubicin (10 mg/kg) in nine doses over 12 weeks. NC-6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC-6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin-treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC-6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC-6300 in patients with hepatocellular carcinoma or other cancers.

K-912（NC-6300）の概要 K-912（NC-6300）は、世界的に幅広く使用されているアントラサイクリン系の抗が ん剤の一つであるエピルビシンを内包したミセル化ナノ粒子製剤で、その特性により、 エピルビシンの有する心毒性の軽減が期待できます。さらに、pH 応答性システムを採 用することで、腫瘍細胞内でのエピルビシンの放出量を高め、既存のエピルビシンに比 べより強力な抗腫瘍効果が期待できます。

Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in the US andPharmorubicin or Epirubicin Ebewe elsewhere.

Similarly to other anthracyclines, epirubicin acts by intercalating DNA strands. Intercalation results in complex formation which inhibits DNA and RNA synthesis. It also triggers DNA cleavage by topoisomerase II, resulting in mechanisms that lead to cell death. Binding to cell membranes and plasma proteins may be involved in the compound’s cytotoxic effects. Epirubicin also generates free radicalsthat cause cell and DNA damage.

Epirubicin is favoured over doxorubicin, the most popular anthracycline, in some chemotherapy regimens as it appears to cause fewer side-effects. Epirubicin has a different spatial orientation of the hydroxyl group at the 4′ carbon of the sugar – it has the opposite chirality – which may account for its faster elimination and reduced toxicity. Epirubicin is primarily used against breast and ovarian cancer, gastric cancer, lung cancer and lymphomas.

Development history

The first trial of epirubicin in humans was published in 1980.^[1] Upjohn applied for approval by the U.S. Food and Drug Administration(FDA) in node-positive breast cancer in 1984, but was turned down because of lack of data.^[2] It appears to have been licensed for use in Europe from around this time however.^[3] In 1999 Pharmacia (who had by then merged with Upjohn) received FDA approval for the use of epirubicin as a component of adjuvant therapy in node-positive patients.

Patent protection for epirubicin expired in August 2007.

References

External links

• http://www.bccancer.bc.ca/HPI/DrugDatabase/DrugIndexPro/Epirubicin.htm
• http://www.pfizerpro.com/page_not_found?rid=/wyeth_html/home/minisites/oncology/ellence/pi/description.html

1H NMR PREDICT

13C NMR PREDICT

COSY

1H NMR

Epirubicin

Systematic (IUPAC) name
(8R,10S)-10-((2S,4S,5R,6S)-4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione
Clinical data
Trade names	Ellence
AHFS/Drugs.com	monograph
MedlinePlus	a603003
Pregnancy category	D (Au, U.S.)
Legal status	℞-only (U.S.), POM (UK)
Routes of administration	Intravenous
Pharmacokinetic data
Bioavailability	NA
Protein binding	77%
Metabolism	Hepatic glucuronidationand oxidation
Excretion	Biliary and renal
Identifiers
CAS Registry Number	56420-45-2
ATC code	L01DB03
PubChem	CID 41867
DrugBank	DB00445
ChemSpider	38201
UNII	3Z8479ZZ5X
KEGG	D07901
ChEBI	CHEBI:47898
ChEMBL	CHEMBL417
Chemical data
Formula	C27H29NO11
Molecular mass	543.519 g/mol

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P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.