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

被引：56

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

共 48 条

[1] Synthesis of the next-generation therapeutic antibodies that combine cell targeting and antibody-catalyzed prodrug activation
Abraham, Sunny
Guo, Fang
Li, Lian-Sheng
Rader, Christoph
Liu, Cheng
Barbas, Carlos F., III
Lerner, Richard A.
Sinha, Subhash C.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (13) : 5584 - 5589
[2] Bosslet K, 1998, CANCER RES, V58, P1195
[3] Bosslet K., 1995, Tumor Targeting, V1, P45
[4] PROTEASE-ACTIVATED PRODRUGS FOR CANCER-CHEMOTHERAPY
CARL, PL
CHAKRAVARTY, PK
KATZENELLENBOGEN, JA
WEBER, MJ
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (04): : 2224 - 2228
[5] MDA-MB-435 and M14 Cell Lines: Identical but not M14 Melanoma?
Chambers, Ann F.
[J]. CANCER RESEARCH, 2009, 69 (13) : 5292 - 5293
[6] Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase
Chen, JM
Dando, PM
Rawlings, ND
Brown, MA
Young, NE
Stevens, RA
Hewitt, E
Watts, C
Barrett, AJ
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (12) : 8090 - 8098
[7] Activation of human prolegumain by cleavage at a C-terminal asparagine residue
Chen, JM
Fortunato, M
Barrett, AJ
[J]. BIOCHEMICAL JOURNAL, 2000, 352 : 327 - 334
[8] Cloning and expression of mouse legumain, a lysosomal endopeptidase
Chen, JM
Dando, PM
Stevens, RAE
Fortunato, M
Barrett, AJ
[J]. BIOCHEMICAL JOURNAL, 1998, 335 : 111 - 117
[9] Expression of the cysteine protease legumain in vascular lesions and functional implications in atherogenesis
Clerin, Valerie
Shih, Heather H.
Deng, Nanhua
Hebert, Gustave
Resmini, Christine
Shields, Kathleen M.
Feldman, Jeffrey L.
Winkler, Aaron
Albert, Leo
Maganti, Vasu
Wong, Anthony
Paulsen, Janet E.
Keith, James C., Jr.
Vlasuk, George P.
Pittman, Debra D.
[J]. ATHEROSCLEROSIS, 2008, 201 (01) : 53 - 66
[10] de Groot FMH, 2001, CURR MED CHEM, V8, P1093

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