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

  • J Med Chem. 2007 May 17;50(10):2289-92. doi: 10.1021/jm0700924.
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
PMID: 17451235 DOI: 10.1021/jm0700924
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.