A small molecule that binds Hedgehog and blocks its signaling in human cells
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Open Access
- 18 January 2009
- journal article
- research article
- Published by Springer Nature in Nature Chemical Biology
- Vol. 5 (3), 154-156
- https://doi.org/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.Keywords
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