Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors.

@article{Blake2012DiscoveryAP,
  title={Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors.},
  author={James F. Blake and Rui Xu and Josef R Bencsik and Dengming Xiao and Nicholas C. Kallan and Stephen T Schlachter and I S Mitchell and Keith L Spencer and Anna L Banka and Eli M. Wallace and Susan L. Gloor and Matthew Martinson and Richard D Woessner and Guy P. A. Vigers and Barbara J. Brandhuber and Jun Liang and Brian S Safina and Jun Li and Birong Zhang and Christine Chabot and Steven Do and Leslie J. Lee and Jason Oeh and Deepak Sampath and Brian B. Lee and Kui Lin and Bianca M. Liederer and Nicholas J. Skelton},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 18},
  pages={8110-27}
}
The discovery and optimization of a series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine compounds that are ATP-competitive, selective inhibitors of protein kinase B/Akt is reported. The initial design and optimization was guided by the use of X-ray structures of inhibitors in complex with Akt1 and the closely related protein kinase A. The resulting compounds demonstrate potent inhibition of all three Akt isoforms in biochemical assays and poor inhibition of other members of the cAMP-dependent… CONTINUE READING
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