Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 19, Issue 8, Pages 2603-2614Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2011.03.013
Keywords
Heat shock protein 90; PU-H71; NVP-AUY922; SNX-2112; Cancer; Docking
Funding
- Commonwealth Cancer Foundation for Research
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center (MSKCC)
- NIH [1R01CA 155226-01, U01AG032969-01A1, R21AG028811, 3P30CA008748-44S2]
- Leukemia and Lymphoma Society LLS [6114-10]
- Byrne Fund
- Geoffrey Beene Cancer Research Center of MSKCC
- Hirshberg Foundation for Pancreatic Cancer Research
- Clinical and Translational Science Center at Weill Cornell Medical College [UL1RR024996]
- Susan G. Komen for the Cure
Ask authors/readers for more resources
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. (C) 2011 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available