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. 2007 Jan 15;67(2):573-9.
doi: 10.1158/0008-5472.CAN-06-2726.

An antagonist of dishevelled protein-protein interaction suppresses beta-catenin-dependent tumor cell growth

Naoaki Fujii  1 , Liang You, Zhidong Xu, Kazutsugu Uematsu, Jufang Shan, Biao He, Iwao Mikami, Lillian R Edmondson, Geoffrey Neale, Jie Zheng, R Kiplin Guy, David M Jablons
Affiliations

An antagonist of dishevelled protein-protein interaction suppresses beta-catenin-dependent tumor cell growth

Naoaki Fujii et al. Cancer Res. .

Erratum in

  • Cancer Res. 2007 Mar 1;67(5):2389

Abstract

Recent progress in the development of inhibitors of protein-protein interactions has opened the door for developing drugs that act by novel and selective mechanisms. Building on that work, we designed a small-molecule inhibitor of the Wnt signaling pathway, which is aberrantly activated across a wide range of human tumors. The compound, named FJ9, disrupts the interaction between the Frizzed-7 Wnt receptor and the PDZ domain of Dishevelled, down-regulating canonical Wnt signaling and suppressing tumor cell growth. The antitumorigenic effects of FJ9 were pronounced, including induction of apoptosis in human cancer cell lines and tumor growth inhibition in a mouse xenograft model. FJ9 is thus among the first non-peptide inhibitors to show therapeutic efficacy through disruption of PDZ protein-protein interactions.

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