A Small-Molecule Agonist of the Wnt Signaling Pathway

Authors

  • Jun Liu Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR202, La Jolla, CA 92037, USA, Fax.: (+1) 858-784-9440
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  • Xu Wu Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR202, La Jolla, CA 92037, USA, Fax.: (+1) 858-784-9440
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    • These authors contributed equally to this paper.

  • Brian Mitchell Dr.,

    1. The Salk Institute for Biological Studies, P.O. Box 85800, La Jolla, California 92186, USA
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    • These authors contributed equally to this paper.

  • Chris Kintner Dr.,

    1. The Salk Institute for Biological Studies, P.O. Box 85800, La Jolla, California 92186, USA
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  • Sheng Ding Dr.,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR202, La Jolla, CA 92037, USA, Fax.: (+1) 858-784-9440
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  • Peter G. Schultz Dr.

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, SR202, La Jolla, CA 92037, USA, Fax.: (+1) 858-784-9440
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  • This work was supported by the Novartis Research Foundation and the Skaggs Institute for Chemical Biology (P.G.S.). We thank Dr. Xiang-ju Gu and Dr. Carsten Andersen for various reagents and technical assistance in GSK-3β kinase assays. This is manuscript 16945-CH of the Scripps Research Institute.

Abstract

original image

A new tool for developmental biology: A screen of combinatorial chemical libraries identified the 2-amino-4,6-disubstituted pyrimidine 1 as a dose-dependent agonist of Wnt signaling. Tadpoles that developed from embryos treated with 1 had substantial head defects (see right-hand image; left=control). Compound 1 appears to mimic the effects of a Wnt ligand in a Xenopus model and may be a useful tool in the study of physiological processes that involve the Wnt pathway.

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