Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design†
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- 作者：Douglas S. Williamson* ; Jenifer Borgognoni ; Alexandra Clay ; Zoe Daniels ; Pawel Dokurno ; Martin J. Drysdale ; Nicolas Foloppe ; Geraint L. Francis ; Christopher J. Graham ; Rob Howes ; Alba T. Macias ; James
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：March 26, 2009
- 年：2009
- 卷：52
- 期：6
- 页码：1510-1513
- 全文大小：195K
- 年卷期：v.52,no.6(March 26, 2009)
- ISSN：1520-4804
文摘
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.