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WIKI4, a Novel Inhibitor of Tankyrase and Wnt/ß-catenin Signaling

WIKI4, a Novel Inhibitor of Tankyrase and Wnt/ß-catenin Signaling

Richard G James, Kathryn C Davidson, Katherine A Bosch, Travis L Biechele, Nicholas C Robin, Russell J Taylor, Michael B Major, Nathan D Camp, Kerry Fowler, Timothy J Martins, Randall T Moon

PLoS One. 2012;7(12):e50457.

PMID: 23227175

Abstract:

The Wnt/ß-catenin signaling pathway controls important cellular events during development and often contributes to disease when dysregulated. Using high throughput screening we have identified a new small molecule inhibitor of Wnt/ß-catenin signaling, WIKI4. WIKI4 inhibits expression of ß-catenin target genes and cellular responses to Wnt/ß-catenin signaling in cancer cell lines as well as in human embryonic stem cells. Furthermore, we demonstrate that WIKI4 mediates its effects on Wnt/ß-catenin signaling by inhibiting the enzymatic activity of TNKS2, a regulator of AXIN ubiquitylation and degradation. While TNKS has previously been shown to be the target of small molecule inhibitors of Wnt/ß-catenin signaling, WIKI4 is structurally distinct from previously identified TNKS inhibitors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP838818261	WIKI4		838818-26-1	Price

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