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

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

Peng, Lee F; Schreiber, Stuart L; Stanton, Benjamin Z; Maloof, Nicole; Nakai, Kazuo; Wang, Xiang; Duffner, Jay L; Taveras, Kennedy M; Hyman, Joel M; Lee, Sam W; Koehler, Angela N; Chen, James K; Fox, Julia L; Mandinova, Anna

Nature chemical biology, 03/2009, Volume: 5, Issue: 3

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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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