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ID: ALA1146822

Journal: Bioorg Med Chem Lett

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

Authors: Dymock B, Barril X, Beswick M, Collier A, Davies N, Drysdale M, Fink A, Fromont C, Hubbard RE, Massey A, Surgenor A, Wright L.

Abstract: Multiple 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.

CiteXplore: 14698151

DOI: 10.1016/j.bmcl.2003.11.011