The Legumain Protease-Activated Auristatin Prodrugs Suppress Tumor Growth and Metastasis without Toxicity

被引：57

作者：

Bajjuri, Krishna Mohan ^{[1
,2
]}

Liu, Yuan ^{[3
]}

Liu, Cheng ^{[3
]}

Sinha, Subhash C. ^{[1
,2
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

来源：

CHEMMEDCHEM | 2011年 / 6卷 / 01期

关键词：

auristatins; cytotoxins; legumain; prodrugs; proteases; ASPARAGINE ENDOPEPTIDASE; SELECTIVE CHEMOTHERAPY; ANTINEOPLASTIC AGENTS; ALDOLASE ANTIBODY; CANCER; POTENT; FIBRONECTIN; MDA-MB-435; EXPRESSION; INHIBITORS;

D O I：

10.1002/cmdc.201000478

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tumor exploitation: Novel monomethylauristatin E and didesmethylauristatin E prodrugs were prepared, and in vitro and in vivo evaluations of the prodrugs using human and mouse cancer cell lines showed that they are less toxic and more efficacious than the parent cytotoxins, as their activation was catalyzed selectively by the cysteine protease, legumain, which is overexpressed in the active form in tumor microenvironments. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：54 / 59

页数：6

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