Title:
HSP90に結合するための小分子組成物
Document Type and Number:
Japanese Patent JP2005519848
Kind Code:
A
Abstract:
Structural differences in binding pockets of members of the HSP90 family can be exploited to achieve differential degradation of kinases and other signaling proteins through the use of designed small molecules which interact with the N-terminal binding pocket with an affinity which is greater than ADP and different from the ansamycin antibiotics for at least one species of the HSP90 family. Moreover, these small molecules can be designed to be soluble in aqueous media, thus providing a further advantage over the use of ansamycin antibiotics. Pharmaceutical compositions can be formulated containing a pharmaceutically acceptable carrier and a molecule that includes a binding moiety which binds to the N-terminal pocket of at least one member of the HSP90 family of proteins. Such binding moieties were found to have antiproliferative activity against tumor cells which are dependent on proteins requiring chaperones of the HSP90 family for their function. Different chemical species have different activity, however, allowing the selection of, for example Her2 degradation without degradation of Raf kinase. Thus, the binding moieties possess an inherent targeting capacity. In addition, the small molecules can be linked to targeting moieties to provide targeting of the activity to specific classes of cells. Thus, the invention further provides a method for treatment of diseases, including cancers, by administration of these compositions. Dimeric forms of the binding moieties may also be employed.
Inventors:
Thiosis, gabriella
Neil Rosen
Neil Rosen
Application Number:
JP2002538887D
Publication Date:
July 07, 2005
Filing Date:
November 01, 2001
Export Citation:
Assignee:
SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH
International Classes:
G01N33/53; A61K31/52; A61K45/00; A61P35/00; A61P43/00; C07D209/36; C07D473/00; C07D473/34; C07D473/40; C07K14/47; G01N33/15; G01N33/566; (IPC1-7): A61K45/00; A61K31/52; A61P35/00; C07D473/34; G01N33/15; G01N33/53; G01N33/566
Attorney, Agent or Firm:
Masayoshi Misawa