Structure–activity relationship studies of small-molecule inhibitors of Wnt response

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Abstract

Suppression of oncogenic Wnt-mediated signaling holds promise as an anti-cancer therapeutic strategy. We previously reported a novel class of small molecules (IWR-1/2, inhibitors of Wnt response) that antagonize Wnt signaling by stabilizing the Axin destruction complex. Herein, we present the results of structure-activity relationship studies of these compounds.

Graphical abstract

SAR studies of IWR-1 are described.

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Acknowledgments

We thank UT Southwestern Medical Center, NIH (NCI P01-CA095471, NIGMS R01-GM079554, NIGMS R01-GM076398), American Cancer Society (RSG GMC-112251) and Welch Foundation (I-1596, I-1665) for financial support. L.L. is a Virginia Murchison Linthicum Scholar in Medical Research and C.C. is a Southwestern Medical Foundation Scholar in Biomedical Research. We thank Michael Dodge for critical reading of this Letter.

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