LEURUBICIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H40N2O12
Molecular Weight	656.6769
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(C[C@H](NC(=O)[C@@H](N)CC(C)C)[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=HROXIDVVXKDCBD-ZUWKMVCBSA-N

InChI=1S/C33H40N2O12/c1-13(2)8-17(34)32(43)35-18-9-22(46-14(3)27(18)38)47-20-11-33(44,21(37)12-36)10-16-24(20)31(42)26-25(29(16)40)28(39)15-6-5-7-19(45-4)23(15)30(26)41/h5-7,13-14,17-18,20,22,27,36,38,40,42,44H,8-12,34H2,1-4H3,(H,35,43)/t14-,17-,18-,20-,22-,27+,33-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C33H40N2O12
Molecular Weight	656.6769
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18194838 | https://www.ncbi.nlm.nih.gov/pubmed/1451235 | https://www.ncbi.nlm.nih.gov/pubmed/1544285

Leurubicin was developed as a prodrug of doxorubicin (Dox) with the aim of lowering the cardiotoxicity and improving the therapeutic index produced by Dox. Antineoplastic agent Dox was rapidly formed from leurubicin, reaching peak levels in plasma within 5 min and in tissues within 1 h after i.v. administration of leurubicin. The incorporation of leurubicin into the MES-SA human uterine sarcoma cell line and its Dox resistant counterpart, MES-SA/Dx5 cell line and the subsequent transformation of leurubicin into Dox and its subcellular distribution, were investigated. In both cell lines the cellular uptakes of Dox and leurubicin were similar at equimolar doses, while the percent transformation of leurubicin into Dox in MES-SA/Dx5 cells was about twice as great as its transformation in MES-SA cells, which is beneficial for reaching Dox cytotoxic levels in this resistant cell line. The highest Dox/ leurubicin ratio was found in the nuclear fraction, followed by the ratio in the low density organelle fraction that contains lysosomes, organelles in which lysosomal hydrolytic enzymes, capthesins, transform leurubicin into Dox.

Approval Year

PubMed

Title	Date	PubMed
Cardiotoxicity and comparative pharmacokinetics of six anthracyclines in the rabbit.	1980 Oct	6934026
Selective uptake of a toxic lipophilic anthracycline derivative by the low-density lipoprotein receptor pathway in cultured fibroblasts.	1985 Apr	3856679
The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine-isoleucinate in human ovarian cancer xenografts.	1992 Dec	1457343
Plasma pharmacokinetics and pharmacodynamics of a new prodrug N-l-leucyldoxorubicin and its metabolites in a phase I clinical trial.	1992 Dec	1453205
Human pharmacokinetics of N-L-leucyl-doxorubicin, a new anthracycline derivative, and its correlation with clinical toxicities.	1992 Mar	1544285
Aspects of the cellular pharmacology of N-l-leucyldoxorubicin in human tumor cell lines.	1993 May 5	8494552
The antitumour activity of the prodrug N-L-leucyl-doxorubicin and its parent compound doxorubicin in human tumour xenografts.	1998 Sep	9893636
Superior therapeutic efficacy of N-L-leucyl-doxorubicin versus doxorubicin in human melanoma xenografts correlates with higher tumour concentrations of free drug.	1999 Jul	10533461
Extracellularly tumor-activated prodrugs for the selective chemotherapy of cancer: application to doxorubicin and preliminary in vitro and in vivo studies.	2001 Apr 1	11306455
Monitoring incorporation, transformation and subcellular distribution of N-l-leucyl-doxorubicin in uterine sarcoma cells using capillary electrophoretic techniques.	2008 Apr 8	18194838
Monitoring subcellular biotransformation of N-L-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection.	2014 Apr	24573576

Patents

Sample Use Guides

In Vivo Use Guide

30 to 240 mg/m2

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:30:44 GMT 2023` Edited by `admin` on `Fri Dec 15 16:30:44 GMT 2023`
Record UNII	1Z20MGK851
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LEURUBICIN

Official Name

English

(8S,10S)-10-((3-((S)-2-AMINO-4-METHYLVALERAMIDO)-2,3,6-TRIDEOXY-.ALPHA.-L-LYXO-HEXOPYRANOSYL)OXY)-8-GLYCOLOYL-7,8,9,10-TETRAHYDRO-6,8,11-TRIHYDROXY-1-METHOXY-5,12-NAPHTHACENEDIONE

Common Name

English

leurubicin [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1594