AMRUBICIN

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H25NO9
Molecular Weight	483.4673
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[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=VJZITPJGSQKZMX-XDPRQOKASA-N

InChI=1S/C25H25NO9/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/t14-,15+,16-,17-,25-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H25NO9
Molecular Weight	483.4673
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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	Inhibitor 8,297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Small-cell lung cancer 41	Primary		Approved 8,429	CALSED
Non-small cell lung cancer 206	Primary		Approved 8,429	CALSED

C_max

Value	Dose	Analyte	Population
3407 ng/mL	45 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
4869 ng/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
3349 ng/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
1867 ng/mL	30 mg/m² multiple, intravenous	AMRUBICIN plasma	Homo sapiens
94 ng/mL	45 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
333 ng/mL	40 mg/m² 1 times / day multiple, oral	AMRUBICINOL plasma	Homo sapiens
162 ng/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
87 ng/mL	30 mg/m² multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
1693 ng/mL	30 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
3414 ng/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
4869 ng/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
77 ng/mL	30 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
170 ng/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
333 ng/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
3329 ng/mL	40 mg/m² single, intravenous	AMRUBICIN plasma	Homo sapiens
4024 ng/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
26.8 ng/mL	40 mg/m² single, intravenous	AMRUBICINOL plasma	Homo sapiens
42.5 ng/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
7290 ng/mL	65 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
7919 ng/mL	60 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
64.9 ng/mL	65 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
44.8 ng/mL	60 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
13490 ng × h/mL	45 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
16706 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
13447 ng × h/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
10262 ng × h/mL	30 mg/m² multiple, intravenous	AMRUBICIN plasma	Homo sapiens
2585 ng × h/mL	45 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
4097 ng × h/mL	40 mg/m² 1 times / day multiple, oral	AMRUBICINOL plasma	Homo sapiens
2325 ng × h/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
1514 ng × h/mL	30 mg/m² multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
8601 ng × h/mL	30 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
13071 ng × h/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
16706 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
1361 ng × h/mL	30 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
2476 ng × h/mL	35 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
4097 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
1968 ng × h/mL	40 mg/m² single, intravenous	AMRUBICIN plasma	Homo sapiens
2152 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
378 ng × h/mL	40 mg/m² single, intravenous	AMRUBICINOL plasma	Homo sapiens
624 ng × h/mL	40 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
5279 ng × h/mL	65 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
5737 ng × h/mL	60 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
265 ng × h/mL	65 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
378 ng × h/mL	60 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
4.7 h	30 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
7.1 h	35 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
7.4 h	40 mg/m² 1 times / day multiple, intravenous	AMRUBICIN plasma	Homo sapiens
13.8 h	30 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
18 h	35 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
17.9 h	40 mg/m² 1 times / day multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
4.66 h	65 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
3.63 h	60 mg/m² 1 times / week multiple, intravenous	AMRUBICIN plasma	Homo sapiens
13.3 h	65 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens
13.39 h	60 mg/m² 1 times / week multiple, intravenous	AMRUBICINOL plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT	Other AEs: Febrile neutropenia, Arrhythmia...
50 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT	Other AEs: leukopenia, Neutropenia...
65 mg/m2 1 times / week multiple, intravenous MTD	unhealthy, ADULT	Other AEs: Aspartate aminotransferase increase, Alanine aminotransferase increase...
30 mg/m2 1 times / day multiple, intravenous Studied dose	unhealthy, ADULT	Other AEs: Thrombocytopenia...
35 mg/m2 1 times / day multiple, intravenous RP2D	unhealthy	Other AEs: Febrile neutropenia, Thrombocytopenia...

Showing 1 to 5 of 5 entries

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AEs

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AE	Significance	Dose	Population
Arrhythmia	grade 3, 1 pt	40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT
Febrile neutropenia	grade 3, 1 pt	40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT
Neutropenia	grade 4, 1 pt	40 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT
Hematemesis	3 patients	50 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT
Melaena	3 patients	50 mg/m2 1 times / day multiple, intravenous MTD	unhealthy, ADULT

Showing 1 to 5 of 17 entries

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PubMed

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Title	Date	PubMed
Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents.	2002 Jul	12114451
[Recent progress in the treatment of ED small cell lung cancer].	2002 May	12101718
[Development of an individualized therapy for establishing the optimal dosage by the pharmacokinetics profiles of anticancer agents].	2005 Aug	16079613
Small-cell lung cancer: current therapy and novel agents.	2005 Jan	15743151
Pharmacokinetics of amrubicin and its active metabolite amrubicinol in lung cancer patients.	2006 Feb	16418698

Showing 1 to 5 of 13 entries

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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.

Substance Class	Chemical
Record UNII	93N13LB4Z2
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

AMRUBICIN

Official Name

English

Amrubicin [WHO-DD]

Common Name

English

AMRUBICIN [USAN]

Common Name

English

AMRUBICIN [MI]

Common Name

English

amrubicin [INN]

Common Name

English

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Classification Tree

Code System

Code

Anthracyclines and related substances

WHO-ATC

L01DB10

Designated/Withdrawn

FDA ORPHAN DRUG

255307

Anthracyclines and related substances

WHO-VATC

QL01DB10

DNA Minor Groove Binding Agent

NCI_THESAURUS

C1594

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Code System

Code

Type

Description

NCI_THESAURUS

C80089

PRIMARY

MERCK INDEX

m1858

PRIMARY

Merck Index

MESH

C055866

PRIMARY

PUBCHEM

3035016

PRIMARY

WIKIPEDIA

AMRUBICIN

PRIMARY

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Related Record

Type

Details


					EUL6MP8FZW

AMRUBICIN HYDROCHLORIDE

SALT/SOLVATE -> PARENT

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Related Record

Type

Details


					93N13LB4Z2

AMRUBICIN

ACTIVE MOIETY

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2