Journal of Medicinal Chemistry 2007-05-17

Rapid evolution of 6-phenylpurine inhibitors of protein kinase B through structure-based design.

Alastair Donald, Tatiana McHardy, Martin G Rowlands, Lisa-Jane K Hunter, Thomas G Davies, Valerio Berdini, Robert G Boyle, G Wynne Aherne, Michelle D Garrett, Ian Collins

Index: J. Med. Chem. 50 , 2289-92, (2007)

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Abstract

6-phenylpurines were identified as novel, ATP-competitive inhibitors of protein kinase B (PKB/Akt) from a fragment-based screen and were rapidly progressed to potent compounds using iterative protein-ligand crystallography with a PKA-PKB chimeric protein. An elaborated lead compound showed cell growth inhibition and effects on cellular signaling pathways characteristic of PKB inhibition.


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