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- Title
A small molecule that binds Hedgehog and blocks its signaling in human cells.
- Authors
Stanton, Benjamin Z; Peng, Lee F; 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; Schreiber, Stuart L
- 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.
- Publication
Nature chemical biology, 2009, Vol 5, Issue 3, p154
- ISSN
1552-4469
- Publication type
Journal Article
- DOI
10.1038/nchembio.142