ACS Med Chem Lett
Department of Chemistry, Center for Cell and Genome Science, University of Utah, Salt Lake City, Utah 84112-0850, United States.
Published: May 2016
A small-molecule inhibitor with a 1,4-dibenzoylpiperazine scaffold was designed to match the critical binding elements in the β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction interface. Inhibitor optimization led to a potent inhibitor that can disrupt the β-catenin/BCL9 interaction and exhibit 98-fold selectivity over the β-catenin/cadherin interaction. The binding mode of new inhibitors was characterized by structure-activity relationships and site-directed mutagenesis studies. Cell-based studies demonstrated that this series of inhibitors can selectively suppress canonical Wnt signaling and inhibit growth of Wnt/β-catenin-dependent cancer cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867476 | PMC |
http://dx.doi.org/10.1021/acsmedchemlett.5b00284 | DOI Listing |
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