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Structural analogues of smoothened intracellular loops as potent inhibitors of hedgehog pathway and cancer cell growth

  1. Author:
    Remsberg, J. R.
    Lou, H.
    Tarasov, S. G.
    Dean, M.
    Tarasova, N. I.

  2. Author Address

    NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21701 USA. NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Struct Biophys Lab, Frederick, MD 21701 USA.;Tarasova, NI, NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21701 USA.;tarasova@ncifcrf.gov
    1. Year: 2007
    2. Date: Sep
  2. Journal: Journal of Medicinal Chemistry
    1. 50
    2. 18
    3. Pages: 4534-4538
  4. Type of Article: Article
  5. ISSN: 0022-2623
  1. Abstract:

    Smoothened is a critical component of the Hedgehog pathway that is essential for stem cell renewal and is dysregulated in many cancer types. We have found synthetic analogues of the second and third intracellular loops of smoothened to be potent inhibitors of the Hedgehog pathway. Palmitoylated peptides as short as 10 residues inhibited melanoma cells growth with IC50 in the low nanomolar range. The compounds are promising drug candidates and convenient tools for solving mechanisms of Hedgehog signaling.

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External Sources

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  2. DOI: 10.1021/jm0705657
  3. View record in Web of Science®
  4. WOS: 000249150700026

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