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

doi:10.1038/nchembio.142

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

Broad Institute of Harvard University and Massachusetts Institute of Technology
Harvard University
Stanford University
Massachusetts General Hospital

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	Nature Chemical Biology
Volume	5
Issue number	3
Pages (from-to)	154-156
ISSN	1552-4450
DOIs	https://doi.org/10.1038/nchembio.142
Publication status	Published - 2009
Externally published	Yes

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title = "A small molecule that binds Hedgehog and blocks its signaling in human cells",

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.",

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

year = "2009",

doi = "10.1038/nchembio.142",

language = "English",

volume = "5",

pages = "154--156",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Research",

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T1 - A small molecule that binds Hedgehog and blocks its signaling in human cells

AU - Stanton, Benjamin Z.

AU - Peng, Lee F.

AU - Maloof, Nicole

AU - Nakai, Kazuo

AU - Wang, Xiang

AU - Taveras, Kennedy

AU - Hyman, Joel M.

AU - Lee, Sam W.

AU - Koehler, Angela N.

AU - Chen, James K.

AU - Fox, Julia L.

AU - Mandinova, Anna

AU - Schreiber, Stuart L.

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/nchembio.142

DO - 10.1038/nchembio.142

M3 - Journal article

C2 - 19151731

SN - 1552-4450

VL - 5

SP - 154

EP - 156

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 3

ER -

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

Abstract

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