A small molecule that binds Hedgehog and blocks its signaling in human cells

  • Nat Chem Biol. 2009 Mar;5(3):154-6. doi: 10.1038/nchembio.142.
Benjamin Z Stanton  1 ,  Lee F Peng ,  Nicole Maloof ,  Kazuo Nakai ,  Xiang Wang ,  Jay L Duffner ,  Kennedy M Taveras ,  Joel M Hyman ,  Sam W Lee ,  Angela N Koehler ,  James K Chen ,  Julia L Fox ,  Anna Mandinova ,  Stuart L Schreiber
Affiliations
  • 1. Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
PMID: 19151731 DOI: 10.1038/nchembio.142
Abstract

Small-molecule inhibition of extracellular proteins that activate membrane receptors has proven to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic Hedgehog (Shh) protein and blocks Shh signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched.

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