Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.
Article Details
- CitationCopy to clipboard
Williamson DS, Borgognoni J, Clay A, Daniels Z, Dokurno P, Drysdale MJ, Foloppe N, Francis GL, Graham CJ, Howes R, Macias AT, Murray JB, Parsons R, Shaw T, Surgenor AE, Terry L, Wang Y, Wood M, Massey AJ
Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design.
J Med Chem. 2009 Mar 26;52(6):1510-3. doi: 10.1021/jm801627a.
- PubMed ID
- 19256508 [ View in PubMed]
- Abstract
The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.