Fragment‐based Identification of Hsp90 Inhibitors

Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high‐concentration biochemical assay, as well as its optimisation by in sil...

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Bibliographic Details
Published in:ChemMedChem 2009-06, Vol.4 (6), p.963-966
Main Authors: Barker, John J., Barker, Oliver, Boggio, Roberto, Chauhan, Viddhata, Cheng, Robert K. Y., Corden, Vincent, Courtney, Stephen M., Edwards, Neil, Falque, Virginie M., Fusar, Fulvia, Gardiner, Mihaly, Hamelin, Estelle M. N., Hesterkamp, Thomas, Ichihara, Osamu, Jones, Richard S., Mather, Owen, Mercurio, Ciro, Minucci, Saverio, Montalbetti, Christian A. G. N., Müller, Annett, Patel, Deepti, Phillips, Banu G., Varasi, Mario, Whittaker, Mark, Winkler, Dirk, Yarnold, Christopher J.
Format: Article
Language:English
Subjects:
Binding Sites
Cell Line, Tumor
Computer Simulation
Crystallography, X-Ray
Drug Design
fragment‐based screening
Hsp90
HSP90 Heat-Shock Proteins - antagonists & inhibitors
HSP90 Heat-Shock Proteins - metabolism
Humans
oximes
Oximes - chemical synthesis
Oximes - chemistry
Oximes - pharmacology
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Structure-Activity Relationship
structure‐based drug design
tetrahydrobenzopyrimidine
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Summary:Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high‐concentration biochemical assay, as well as its optimisation by in silico searching coupled with a structure‐based drug design (SBDD) approach. Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high‐concentration biochemical assay, as well as its optimisation by in silico searching coupled with a structure‐based drug design (SBDD) approach.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.200900011