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Purmorphamine activates the Hedgehog pathway by targeting Smoothened

Nature Chemical Biology volume 2, pages 29–30 (2006)Cite this article

Abstract

Hedgehog (Hh) signaling is an important regulator of embryonic patterning, tissue regeneration, stem cell renewal and cancer growth. A purine derivative named purmorphamine was previously found to activate the Hh pathway and affect osteoblast differentiation through an unknown mechanism. We demonstrate here that purmorphamine directly targets Smoothened, a critical component of the Hh signaling pathway.

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Figure 1: Small-molecule modulators of the Hh pathway.
Figure 2: Purmorphamine directly targets Smoothened.

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References

  1. Ingham, P.W. & McMahon, A.P. Genes Dev. 15, 3059–3087 (2001).

    Article  CAS  Google Scholar 

  2. Beachy, P.A., Karhadkar, S.S. & Berman, D.M. Nature 432, 324–331 (2004).

    Article  CAS  Google Scholar 

  3. McMahon, A.P., Ingham, P.W. & Tabin, C.J. Curr. Top. Dev. Biol. 53, 1–114 (2003).

    Article  CAS  Google Scholar 

  4. Cooper, M.K., Porter, J.A., Young, K.E. & Beachy, P.A. Science 280, 1603–1607 (1998).

    Article  CAS  Google Scholar 

  5. Chen, J.K., Taipale, J., Cooper, M.K. & Beachy, P.A. Genes Dev. 16, 2743–2748 (2002).

    Article  CAS  Google Scholar 

  6. Chen, J.K. et al. Proc. Natl. Acad. Sci. USA 99, 14071–14076 (2002).

    Article  CAS  Google Scholar 

  7. Frank-Kamenetsky, M. et al. J. Biol. 1, 10 (2002).

    Article  Google Scholar 

  8. Wu, X. et al. J. Am. Chem. Soc. 124, 14520–14521 (2002).

    Article  CAS  Google Scholar 

  9. Wu, X. et al. Chem. Biol. 11, 1229–1238 (2004).

    Article  CAS  Google Scholar 

  10. Taipale, J. et al. Nature 406, 1005–1009 (2000).

    Article  CAS  Google Scholar 

  11. Goodrich, L.V., Milenkovic, L., Higgins, K.M. & Scott, M.P. Science 277, 1109–1113 (1997).

    Article  CAS  Google Scholar 

  12. Ma, Y. et al. Cell 111, 63–75 (2002).

    Article  CAS  Google Scholar 

  13. Denef, N., Neubuser, D., Perez, L. & Cohen, S.M. Cell 102, 521–531 (2000).

    Article  CAS  Google Scholar 

  14. Lum, L. et al. Mol. Cell 12, 1261–1274 (2003).

    Article  CAS  Google Scholar 

  15. Chen, W. et al. Science 306, 2257–2260 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Taipale, Y. Ma, and P. Beachy for providing Smo−/− MEFs. Generation and characterization of this cell line will be described elsewhere (M. Varjosalo, S.-P. Li, and J. Taipale, unpublished data). This work was funded by a Kimmel Scholar Award from the Sidney Kimmel Foundation for Cancer Research.

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  1. Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Surajit Sinha & James K Chen

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  1. Surajit Sinha
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  2. James K Chen
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Correspondence to James K Chen.

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The authors declare no competing financial interests.

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Sinha, S., Chen, J. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol 2, 29–30 (2006). https://doi.org/10.1038/nchembio753

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