Adenosine-Derived Inhibitors of 78 kDa Glucose Regulated Protein (Grp78) ATPase: Insights into Isoform Selectivity

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• 作者：Alba T. Macias ; Douglas S. Williamson ; Nicola Allen ; Jenifer Borgognoni ; Alexandra Clay ; Zoe Daniels ; Pawel Dokurno ; Martin J. Drysdale ; Geraint L. Francis ; Christopher J. Graham ; Rob Howes ; Natalia Matassova ; James B. Murray ; Rachel Parsons ; Terry Shaw ; Allan E. Surgenor ; Lindsey Terry ; Yikang Wang ; Mike Wood ; Andrew J. Massey
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：June 23, 2011
• 年：2011
• 卷：54
• 期：12
• 页码：4034-4041
• 全文大小：972K
• 年卷期：v.54,no.12(June 23, 2011)
• ISSN：1520-4804

文摘

78 kDa glucose-regulated protein (Grp78) is a heat shock protein (HSP) involved in protein folding that plays a role in cancer cell proliferation. Binding of adenosine-derived inhibitors to Grp78 was characterized by surface plasmon resonance and isothermal titration calorimetry. The most potent compounds were 13 (VER-155008) with K_D = 80 nM and 14 with K_D = 60 nM. X-ray crystal structures of Grp78 bound to ATP, ADPnP, and adenosine derivative 10 revealed differences in the binding site between Grp78 and homologous proteins.