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Nat Chem Biol. 2009 Mar;5(3):154-6. doi: 10.1038/nchembio.142. Epub 2009 Jan 18.

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

Author information

  • 1Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.

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.

PMID:
19151731
[PubMed - indexed for MEDLINE]
PMCID:
PMC2770933
Free PMC Article

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