2. Academic Validation
  3. Pyrazolopyrimidines as dual Akt/p70S6K inhibitors

Pyrazolopyrimidines as dual Akt/p70S6K inhibitors

  • Bioorg Med Chem Lett. 2012 Apr 15;22(8):2693-7. doi: 10.1016/j.bmcl.2012.03.011.
Kenneth D Rice 1,  Moon H Kim,  Joerg Bussenius,  Neel K Anand,  Charles M Blazey,  Owen J Bowles,  Lynne Canne-Bannen,  Diva S-M Chan,  Baili Chen,  Erick W Co,  Simona Costanzo,  Steven C DeFina,  Larisa Dubenko,  Stefan Engst,  Maurizio Franzini,  Ping Huang,  Vasu Jammalamadaka,  Richard G Khoury,  Rhett R Klein,  A Douglas Laird,  Donna T Le,  Morrison B Mac,  David J Matthews,  David Markby,  Nicole Miller,  John M Nuss,  Jason J Parks,  Tsze H Tsang,  Amy L Tsuhako,  Yong Wang,  Wei Xu
Affiliations

Affiliation

  • 1 Exelixis, 210 E. Grand Avenue, South San Francisco, CA 94080, USA.
PMID: 22450127 DOI: 10.1016/j.bmcl.2012.03.011
Abstract

Activation of the PI3K/Akt/mTOR kinase pathway is frequently associated with human Cancer. Selective inhibition of p70S6Kinase, which is the last kinase in the PI3K pathway, is not sufficient for strong tumor growth inhibition and can lead to activation of upstream proteins including Akt through relief of a negative feedback loop. Targeting multiple sites in the PI3K pathway might be beneficial for optimal activity. In this manuscript we report the design of dual Akt/p70S6K inhibitors and the evaluation of the lead compound 11b in vivo, which was eventually advanced into clinical development.

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