AMRUBICIN HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H25NO9.ClH
Molecular Weight	519.928
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.[H][C@@]1(C[C@H](O)[C@H](O)CO1)O[C@H]2C[C@@](N)(CC3=C(O)C4=C(C(=O)C5=CC=CC=C5C4=O)C(O)=C23)C(C)=O

InChI

InChIKey=BHMLHEQFWVQAJS-IITOGVPQSA-N

InChI=1S/C25H25NO9.ClH/c1-10(27)25(26)7-13-18(16(8-25)35-17-6-14(28)15(29)9-34-17)24(33)20-19(23(13)32)21(30)11-4-2-3-5-12(11)22(20)31;/h2-5,14-17,28-29,32-33H,6-9,26H2,1H3;1H/t14-,15+,16-,17-,25-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26750506 | https://mink.nipponkayaku.co.jp/product/di/in_file/sedi_cali_in.pdf

Amrubicin is a totally synthetic 9-aminoanthracycline anticancer drug, which is approved in Japan for the treatment of small cell and non-small cell lung cancer. Upon administration amrubicin is reduced to its C-13 hydroxy metabolite, amrubicinol. The cytotoxicity of amrubicinol in vitro is 10 to 100 times greater than that of amrubicin. Thus, the anticancer activity of amrubicin is considered to derive from this active metabolite. The mechanism of action of the drug is related to the inhibition of topoisomerase II by stabilizing the cleavable complex.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase II 66 Target ID: CHEMBL2094255 Sources: https://mink.nipponkayaku.co.jp/product/di/in_file/sedi_cali_in.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Small-cell lung cancer 41 Sources: https://mink.nipponkayaku.co.jp/product/di/in_file/sedi_cali_in.pdf	Primary		Approved 8429	CALSED Approved Use Non small cell lung cancer, small cell lung cancer. Launch Date 2002
Non-small cell lung cancer 206 Sources: https://mink.nipponkayaku.co.jp/product/di/in_file/sedi_cali_in.pdf	Primary		Approved 8429	CALSED Approved Use Non small cell lung cancer, small cell lung cancer Launch Date 2002

PubMed

Title	Date	PubMed
Modern management of small-cell lung cancer.	2007	17927281
[A case of small cell lung cancer under hemodialysis with chronic renal failure treated with amrubicin while measuring blood concentration of the drug].	2007 Apr	17491313
Evaluation of the recommended dose and efficacy of amrubicin as second- and third-line chemotherapy for small cell lung cancer.	2007 Aug	17762341
[A case of relapsed small-cell lung cancer successfully treated by administration of amrubicin].	2007 Dec	18186244
[Analysis of adverse events of amrubicin hydrochloride for pretreated lung cancer patients].	2007 Nov	18030011
Amrubicin for non-small-cell lung cancer and small-cell lung cancer.	2007 Oct	17628745
Dose escalation study of amrubicin in combination with fixed-dose irinotecan in patients with extensive small-cell lung cancer.	2008	18536524
Small cell carcinoma of the prostate treated with amrubicin.	2008 Apr	18463964
Sequential treatment with SN-38 followed by 5-fluorouracil shows synergistic cytotoxic activity in small cell lung cancer cells.	2008 Apr	18357380
[Our clinical experiences of amrubicin hydrochloride monotherapy in extensive-disease small cell lung cancer].	2008 Feb	18281764
Role of P-glycoprotein in accumulation and cytotoxicity of amrubicin and amrubicinol in MDR1 gene-transfected LLC-PK1 cells and human A549 lung adenocarcinoma cells.	2008 Feb 15	18054347
Current status of clinical trials for small cell lung cancer.	2008 Jan	18474014
Pulse gradient, large-volume injection, high-throughput ultra-performance liquid chromatographic/tandem mass spectrometry bioanalysis for measurement of plasma amrubicin and its metabolite amrubicinol.	2008 Jun 6	18452925
Novel systemic therapies for small cell lung cancer.	2008 Mar	18377849
[Two cases of severe myelosuppression from amrubicin in previously-treated small cell lung cancer].	2008 Mar	18347402
[A case of multidrug-resistant squamous cell lung carcinoma responding to S-1 plus CPT-11 combination chemotherapy].	2008 Mar	18347399
Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402.	2008 Nov 20	18854562
Management of small-cell lung cancer: incremental changes but hope for the future.	2008 Nov 30	19133604
Efficacy of amrubicin for non-small cell lung cancer after failure of two or more prior chemotherapy regimens.	2008 Nov-Dec	19192640
[A case of advanced small cell lung cancer complicated by chronic renal failure treated with amrubicin].	2008 Sep	18799918
Effective monotherapy with amrubicin for a refractory extrapulmonary small-cell carcinoma of the liver.	2009	19718248
A case of intimal sarcoma of the pulmonary artery treated with chemoradiotherapy.	2009	19218777
Phase I study of amrubicin and vinorelbine in non-small cell lung cancer previously treated with platinum-based chemotherapy.	2009 Apr	19390943
[Pharmacokinetic study of amrubicin in a case of small lung cancer on hemodialysis].	2009 Aug	19692770
Emerging drugs for small-cell lung cancer.	2009 Dec	19694501
Amrubicin for the treatment of advanced lung cancer.	2009 Feb	19239396
Retrospective analysis of efficacy and safety of amrubicin in refractory and relapsed small-cell lung cancer.	2009 Feb	19225927
Next-generation anthracycline for the management of small cell lung cancer: focus on amrubicin.	2009 Feb 6	19920905
Plasma concentration of amrubicinol in plateau phase in patients treated for 3 days with amrubicin is correlated with hematological toxicities.	2009 Jul	19352172
Thymic small cell carcinoma shows marked response to amrubicin.	2009 Jun	19461410
A phase I study of amrubicin and carboplatin for previously untreated patients with extensive-disease small cell lung cancer.	2009 Jun	19404211
Synergistic cell growth inhibition by the combination of amrubicin and Akt-suppressing tyrosine kinase inhibitors in small cell lung cancer cells: implication of c-Src and its inhibitor.	2009 Mar	19212674
[Second-line treatment and targeted therapy of advanced lung cancer].	2009 May	19461168
Multiple lung metastases presenting as ground-glass opacities in a pulmonary adenocarcinoma: a case report.	2009 May 29	19829882
Amrubicin: a synthetic anthracyclin analogue in the treatment of extensive stage small cell lung cancer.	2009 Nov	19538159
Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.	2009 Nov 13	19915681
[Two cases of recurrent non-small cell lung cancer successfully treated with S-1 as fifth-line chemotherapy].	2009 Oct	19838034
Long-term disease-free survivor of metastatic large-cell neuroendocrine carcinoma of the lung treated with amrubicin and irinotecan.	2009 Sep 21	19920936
A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0405.	2010 Apr	19825887
Co-administration of irinotecan decreases the plasma concentration of an active metabolite of amrubicin, amrubicinol in rats.	2010 Apr	19697031
Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.	2010 Apr 15	20419121
Treatment options for small cell lung cancer - do we have more choice?	2010 Feb 16	20104223
Imatinib mesylate (STI571) enhances amrubicin-induced cytotoxic activity through inhibition of the phosphatidylinositol 3-kinase/Akt pathway in small cell lung cancer cells.	2010 Jan	19956885
Phase II trial of amrubicin for second-line treatment of advanced non-small cell lung cancer: results of the West Japan Thoracic Oncology Group trial (WJTOG0401).	2010 Jan	19884859
A phase II study of amrubicin, a synthetic 9-aminoanthracycline, in patients with previously treated lung cancer.	2010 Jul	19853960
Relationship of mRNA expressions of RanBP2 and topoisomerase II isoforms to cytotoxicity of amrubicin in human lung cancer cell lines.	2010 Jul	19809814
Salvage chemotherapy with amrubicin and platinum for relapsed thymic carcinoma: experience in six cases.	2010 Jun	19415537
The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation.	2010 Mar	20356561
Simple and sensitive HPLC method for determination of amrubicin and amrubicinol in human plasma: application to a clinical pharmacokinetic study.	2010 Mar	19634123
Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer.	2010 May 20	20385980

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose is 45 mg/m2 given intravenously once a day for 3 days.

Route of Administration: Intravenous

In Vitro Use Guide

In a cell viability assay, lung cancer cells DMS 114, NCI-H69, NCI-H82, NCI-H526 were incubated with amrubicin at concentrations from 18 nM to 16 uM for 72 h. IC50 values were 0.803, 1.54, 0.746 and 0.818 uM, respectively.

Name

Type

Language

AMRUBICIN HYDROCHLORIDE

Official Name

English

SM-5887

Code

English

CALSED

Brand Name

English

Amrubicin hydrochloride [WHO-DD]

Common Name

English

AMRUBICIN HYDROCHLORIDE [MI]

Common Name

English

(+)-(7S,9S)-9-ACETYL-9-AMINO-7-((2-DEOXY-.BETA.-D-ERYTHRO-PENTOPYRANOSYL)OXY)-6,11-DIHYDROXY-7,8,9,10-TETRAHYDROTETRACENE-5,12-DIONE HYDROCHLORIDE

Common Name

English

AMRUBICIN HYDROCHLORIDE [JAN]

Common Name

English

SM 5887

Code

English

AMRUBICIN HYDROCHLORIDE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1594