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

…, C Fromont, RE Hubbard, A Massey, A Surgenor…

Index: Dymock, Brian; Barril, Xavier; Beswick, Mandy; Collier, Adam; Davies, Nicholas; Drysdale, Martin; Fink, Alexandra; Fromont, Christophe; Hubbard, Roderick E.; Massey, Andrew; Surgenor, Allan; Wright, Lisa Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 2 p. 325 - 328

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Citation Number: 68

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 ...