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

Nat Chem Biol

Authors	Benjamin Stanton Lee Peng Nicole Maloof Kazuo Nakai Xiang Wang Jay Duffner Kennedy Taveras Joel Hyman Sam Lee Angela Koehler James Chen Julia Fox Anna Mandinova Stuart Schreiber
Keywords	Animals Humans Mice Signal Transduction 3T3 Cells Lactones Receptors, Cell Surface Lactams Drug Discovery Hedgehog Proteins Keratinocytes Patched Receptors
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.
Year of Publication	2009
Journal	Nat Chem Biol
Volume	5
Issue	3
Pages	154-6
Date Published	2009 Mar
ISSN	1552-4469
URL
DOI	10.1038/nchembio.142
PubMed ID	19151731
PubMed Central ID	PMC2770933
Links
Grant list	R01 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