Identification of Inhibitors of Protein Kinase B Using Fragment-Based Lead Discovery
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- 作者：Gordon Saxty ; Steven J. Woodhead ; Valerio Berdini ; Thomas G. Davies ; Marcel L. Verdonk ; Paul G. Wyatt ; Robert G. Boyle ; David Barford ; Robert Downham ; Michelle D. Garrett ; Robin A. Carr
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：May 17, 2007
- 年：2007
- 卷：50
- 期：10
- 页码：2293 - 2296
- 全文大小：278K
- 年卷期：v.50,no.10(May 17, 2007)
- ISSN：1520-4804
文摘
Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80 
M) was identified as a novel, lowmolecular weight inhibitor of protein kinase B (PKB). Herein wedescribe the rapid elaboration of highly potent and ligand efficientanalogues using a fragment growing approach. Iterative structure-baseddesign was supported by protein-ligand structure determinations usinga PKA-PKB "chimera" and a final protein-ligand structure of a leadcompound in PKB
ddle"> itself.
M) was identified as a novel, lowmolecular weight inhibitor of protein kinase B (PKB). Herein wedescribe the rapid elaboration of highly potent and ligand efficientanalogues using a fragment growing approach. Iterative structure-baseddesign was supported by protein-ligand structure determinations usinga PKA-PKB "chimera" and a final protein-ligand structure of a leadcompound in PKBddle"> itself.