Paradoxical activation of Raf by a novel Raf inhibitor.

@article{HallJackson1999ParadoxicalAO,
  title={Paradoxical activation of Raf by a novel Raf inhibitor.},
  author={Clare A Hall-Jackson and Patrick A Eyers and Philip S. Cohen and Michel Goedert and Fiona Boyle and Nicola J. Hewitt and H. J. Plant and Philip J. Hedge},
  journal={Chemistry & biology},
  year={1999},
  volume={6 8},
  pages={559-68}
}
BACKGROUND Raf is a proto-oncogene that is activated in response to growth factors or phorbol esters, and is thought to activate MAP kinase kinase-1 (MKK1) and hence the classical MAP kinase (MAPK) cascade. RESULTS The compound ZM 336372 is identified as a potent and specific inhibitor of Raf isoforms in vitro. Paradoxically, exposure of cells to ZM 336372 induces > 100-fold activation of c-Raf (measured in the absence of compound), but without triggering any activation of MKK1 or p42 MAPK… CONTINUE READING

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