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Nature chemical biology DOI:10.1038/nchembio.142

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

Publication TypeJournal Article
Year of Publication2009
AuthorsStanton, BZ, Peng, LF, Maloof, N, Nakai, K, Wang, X, Duffner, JL, Taveras, KM, Hyman, JM, Lee, SW, Koehler, AN, Chen, JK, Fox, JL, Mandinova, A, Schreiber, SL
JournalNature chemical biology
Volume5
Issue3
Pages154-6
Date Published2009/03/01
ISSN1552-4450
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.

URLhttp://dx.doi.org/10.1038/nchembio.142
DOI10.1038/nchembio.142
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/19151731?dopt=Abstract