2. Academic Validation
  3. A small molecule that binds Hedgehog and blocks its signaling in human cells

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

Affiliation

  • 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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