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A Small-Molecule Antagonist of the Hedgehog Signaling Pathway

Authors

  • Jongkook Lee Dr.,

    1. Dept. of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA, Fax: (+1) 858-784-9440
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  • Xu Wu Dr.,

    1. Genomics Institute of the Novartis Research Foundation, San Dieogo, California 92121, USA
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  • Marina Pasca di Magliano Dr.,

    1. Diabetes Center, Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA
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  • Eric C. Peters Dr.,

    1. Genomics Institute of the Novartis Research Foundation, San Dieogo, California 92121, USA
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  • Yan Wang Dr.,

    1. Genomics Institute of the Novartis Research Foundation, San Dieogo, California 92121, USA
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  • Jiyong Hong Dr.,

    1. Dept. of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA, Fax: (+1) 858-784-9440
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  • Metthias Hebrok Dr.,

    1. Diabetes Center, Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA
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  • Sheng Ding Prof.,

    1. Dept. of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA, Fax: (+1) 858-784-9440
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  • Charles Y. Cho Dr.,

    1. Genomics Institute of the Novartis Research Foundation, San Dieogo, California 92121, USA
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  • Peter G. Schultz Prof.

    1. Dept. of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA, Fax: (+1) 858-784-9440
    2. Genomics Institute of the Novartis Research Foundation, San Dieogo, California 92121, USA
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Abstract

original image

Shadow the Hedgehog. JK184 (illustrated in the scheme) was identified as an antagonist of Hedgehog signaling through a cell-based screen of chemical libraries. Results from biochemical and cellular experiments suggest that JK184 functions by inhibiting class IV alcohol dehydrogenase. This molecule should serve as a useful tool for studying Hedgehog signaling.

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