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Adenine derived inhibitors of the molecular chaperone HSP90-SAR explained through multiple X-ray structures

Posted June 8th, 2010 by pschmidtke
TitleAdenine derived inhibitors of the molecular chaperone HSP90-SAR explained through multiple X-ray structures
Publication TypeJournal Article
Year of Publication2004
AuthorsDymock, B, Barril X, Beswick M, Collier A, Davies N, Drysdale M, Fink A, Fromont C, Hubbard RE, Massey A, Surgenor A, Wright L
JournalBioorganic & medicinal chemistry letters
Volume14
Issue2
Pagination325 - 328
Date Published2004/01/19/
KeywordsAdenine/analogs & derivatives/pharmacology; Cell Line, Tumor; Crystallography, X-Ray/methods; HSP90 Heat-Shock Proteins/antagonists & inhibitors/metabolism; Humans; Molecular Chaperones/antagonists & inhibitors/metabolism; Structure-Activity Relationship
AbstractMultiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors.