Targeted polypharmacology: Discovery of dual inhibitors of tyrosine and phosphoinositide kinases

  title={Targeted polypharmacology: Discovery of dual inhibitors of tyrosine and phosphoinositide kinases},
  author={Beth Apsel and Jimmy A. Blair and Beatriz Z. Gonzalez and Tamim M. Nazif and Morri E. Feldman and Brian D Aizenstein and Randy Hoffman and Roger L Williams and Kevan M. Shokat and Zachary A Knight},
  booktitle={Nature chemical biology},
The clinical success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. It remains unclear to what extent such drugs can be rationally designed, particularly for combinations of targets that are structurally divergent. Here we report the systematic discovery of molecules that potently inhibit both tyrosine kinases and phosphatidylinositol-3-OH kinases, two protein families that are among the most intensely pursued cancer… CONTINUE READING

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A quantitative analysis of kinase inhibitor selectivity

  • Karaman, M.W
  • Nat. Biotechnol
  • 2008

Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity

  • Maira, S.M
  • Mol. Cancer Ther
  • 2008

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