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Drug Discov Today. 2011 Jan;16(1-2):35-41. doi: 10.1016/j.drudis.2010.11.007. Epub 2010 Nov 24.

New avenues to target Wnt/β-catenin signaling.

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Merck Research Laboratories, MSD, Molecular Pharmacology & DMPK, PO Box 20, 5340 BH Oss, The Netherlands.


Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small molecule modulators of Wnt/β-catenin signaling have been identified, none have progressed into clinical trials yet. Recent studies employing genomics and proteomics approaches have yielded more druggable targets, such as kinases and seven-transmembrane receptors. In addition, new assay methods enable a more targeted approach for high-throughput screening of this pathway and are expected to deliver clinical candidates in the coming decade.

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