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

  • Bioorg Med Chem Lett. 2004 Jan 19;14(2):325-8. doi: 10.1016/j.bmcl.2003.11.011.
Brian Dymock  1 ,  Xavier Barril ,  Mandy Beswick ,  Adam Collier ,  Nicholas Davies ,  Martin Drysdale ,  Alexandra Fink ,  Christophe Fromont ,  Roderick E Hubbard ,  Andrew Massey ,  Allan Surgenor ,  Lisa Wright
Affiliations
PMID: 14698151 DOI: 10.1016/j.bmcl.2003.11.011
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.