Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem. 2011 Apr 15;19(8):2603-14. doi: 10.1016/j.bmc.2011.03.013. Epub 2011 Mar 12.

Design, synthesis, and evaluation of small molecule Hsp90 probes.

Author information

1
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States.

Abstract

A number of compounds from different chemical classes are known to bind competitively to the ATP-pocket of Hsp90 and inhibit its chaperone function. The natural product geldanamycin was the first reported inhibitor of Hsp90 and since then synthetic inhibitors from purine, isoxazole and indazol-4-one chemical classes have been discovered and are currently or soon to be in clinical trials for the treatment of cancer. In spite of a similar binding mode to Hsp90, distinct biological profiles were demonstrated among these molecules, both in vitro and in vivo. To better understand the molecular basis for these dissimilarities, we report here the synthesis of chemical tools for three Hsp90 inhibitor classes. These agents will be useful for probing tumor-by-tumor the Hsp90 complexes isolated by specific inhibitors. Such information will lead to better understanding of tumor specific molecular markers to aid in their clinical development. It will also help to elucidate the molecular basis for the biological differences observed among Hsp90 inhibitors.

PMID:
21459002
PMCID:
PMC3143825
DOI:
10.1016/j.bmc.2011.03.013
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center