Journal
NATURE CHEMICAL BIOLOGY
Volume 5, Issue 3, Pages 154-156Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.142
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [R01 CA195534, R01 CA149477, N01CO12400, P01 CA080058, N01 CO012400, N01-CO-12400] Funding Source: Medline
- NIGMS NIH HHS [R01 GM038627-17, GM-38627, R37 GM038627, R01 GM038627] Funding Source: Medline
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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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