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Design, synthesis, and evaluation of small molecule Hsp90 probes
Design, synthesis, and evaluation of small molecule Hsp90 probes
- Source :
- Bioorganicmedicinal chemistry. 19(8)
- Publication Year :
- 2010
-
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 amongst 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.
- Subjects :
- Molecular model
Clinical Biochemistry
Pharmaceutical Science
Antineoplastic Agents
Biochemistry
Chemical synthesis
Binding, Competitive
Article
Hsp90 inhibitor
chemistry.chemical_compound
Drug Discovery
polycyclic compounds
Humans
HSP90 Heat-Shock Proteins
Molecular Biology
Natural product
biology
Organic Chemistry
Geldanamycin
Hsp90
Small molecule
chemistry
Docking (molecular)
Drug Design
Molecular Probes
biology.protein
Molecular Medicine
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 19
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....91a26b820e44d276e66efb89a7206e9f