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

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

Research output: Contribution to journalJournal articleResearchpeer-review


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.
Original languageEnglish
JournalNature Chemical Biology
Issue number3
Pages (from-to)154-156
Publication statusPublished - 2009
Externally publishedYes

Cite this

Stanton, B. Z., Peng, L. F., Maloof, N., Nakai, K., Wang, X., Taveras, K., Hyman, J. M., Lee, S. W., Koehler, A. N., Chen, J. K., Fox, J. L., Mandinova, A., & Schreiber, S. L. (2009). A small molecule that binds Hedgehog and blocks its signaling in human cells. Nature Chemical Biology, 5(3), 154-156. https://doi.org/10.1038/nchembio.142