Synthesis of Hsp90 inhibitor dimers as potential antitumor agents

被引：13

作者：

Muranaka, Kazuhiro ^{[1
]}

Sano, Akiko ^{[2
]}

Ichikawa, Satoshi ^{[1
]}

Matsuda, Akira ^{[1
]}

机构：

[1] Hokkaido Univ, Fac Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan

[2] Taiho Pharmaceut Co Ltd, Hanno Res Ctr, Discovery & Dev Lab 1, Hannou 3578527, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 11期

关键词：

heat shock protein; Hsp90; PU3; anticancer; structure-based drug design;

D O I：

10.1016/j.bmc.2008.04.070

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5862 / 5870

页数：9

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