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Nat Chem Biol 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
JournalNat Chem Biol
Volume5
Issue3
Pages154-6
Date Published2009 Mar
ISSN1552-4469
Keywords3T3 Cells, Animals, Drug Discovery, Hedgehog Proteins, Humans, Keratinocytes, Lactams, Lactones, Mice, Patched Receptors, Receptors, Cell Surface, Signal Transduction
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

Alternate JournalNat. Chem. Biol.
PubMed ID19151731
PubMed Central IDPMC2770933
Grant ListR01 GM038627-17 / GM / NIGMS NIH HHS / United States
R37 GM038627 / GM / NIGMS NIH HHS / United States
R01 CA149477 / CA / NCI NIH HHS / United States
GM-38627 / GM / NIGMS NIH HHS / United States
R01 GM038627 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
P01 CA080058 / CA / NCI NIH HHS / United States
R01 CA195534 / CA / NCI NIH HHS / United States
N01 CO012400 / CO / NCI NIH HHS / United States
N01CO12400 / CA / NCI NIH HHS / United States
N01-CO-12400 / CO / NCI NIH HHS / United States