Title:
ゲルダナマイシンおよび誘導体はガン浸潤を阻害し、新規な標的を同定する
Document Type and Number:
Japanese Patent JP2007530596
Kind Code:
A
Abstract:
Geldanamycin derivatives that block the uPA-plasmin network and inhibit growth and invasion by glioblastoma cells and other tumors at femtomolar concentrations are potentially highly active anti-cancer drugs. GA and various 17-amino-17-demethoxygelddanamycin derivatives are disclosed that block HGF/SF-mediated Met tyrosine kinase receptor-dependent uPA activation at fM levels. Other ansamycins (macbecins I and II), GA derivatives, and radicicol required concentrations several logs higher (>=nM) to achieve such inhibition. The inhibitory activity of tested compounds was discordant with the known ability of drugs of this class to bind to hsp90, indicating the existence of a novel target(s) for HGF/SF-mediated events in tumor development. Methods of using such compounds to inhibit cancer cell activities and to treat tumors are disclosed. Such treatment with low doses of these highly active compounds provide an option for treating various Met-expressing tumors, in particular invasive brain cancers, either alone or in combination with conventional surgery, chemotherapy, or radiotherapy.
Inventors:
Sea, chien
Wenkert, David
Shen, Yuchai
Bande Woode, George F.
High, rick
Wenkert, David
Shen, Yuchai
Bande Woode, George F.
High, rick
Application Number:
JP2007505267A
Publication Date:
November 01, 2007
Filing Date:
March 28, 2005
Export Citation:
Assignee:
Van Andel Research Institute
International Classes:
C07D225/06; A61K31/395; A61K31/396; A61K31/397; A61K31/537; A61K51/00; A61P13/08; A61P35/00; A61P35/04; C07D403/04; C07D498/08
Attorney, Agent or Firm:
Hidesaku Yamamoto
Takaaki Yasumura
Natsuki Morishita
Takaaki Yasumura
Natsuki Morishita