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Targeting Protein-Protein Interactions by Small Molecules pp 239–248Cite as

Small-Molecule Inhibitors for the β-Catenin/T Cell Factor Protein-Protein Interaction

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Abstract

The aberrant activation of canonical Wnt signaling is strongly associated with the initiation and progression of many cancers. Cancer stem cells, which are resistant to conventional chemo- and radiotherapies and especially virulent, are also controlled by the hyperactivation of canonical Wnt signaling. Therefore, the disruption of this signaling pathway represents an attractive strategy for cancer therapy. The formation of the β-catenin/Tcf complex in the cell nucleus is the penultimate step of canonical Wnt signaling; hence, these protein-protein interactions (PPIs) were identified as an appealing therapeutic target for anticancer drug development. Herein, the approaches for the discovery of small-molecule inhibitors to disrupt the β-catenin/T cell factor protein-protein interaction, including high throughput screening (HTS), virtual screening, and hot spots-based rational design, were reviewed and the representative examples were presented. These novel inhibitors provide a good starting point for further research. Furthermore, the challenge and opportunity in this researching area, such as further improvement of the binding potency and selectivity, as well as the development of drug-like inhibitors for cell-based and in vivo studies were also discussed.

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Acknowledgements

We thank the National Natural Science Foundation of China (21602060, Y.-Q. Z. and 21372073, 21738002 and 21572055, W. W.) for the financial support of the research.

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Authors and Affiliations

  1. School of Pharmacy, East China University of Science & Technology, 130 Mei-Long Rd, Shanghai, 200237, China

    Yongqiang Zhang & Wei Wang

  2. Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131, USA

    Wei Wang

Authors
  1. Yongqiang Zhang
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  2. Wei Wang
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Correspondence to Yongqiang Zhang or Wei Wang .

Editor information

Editors and Affiliations

  1. School of Pharmacy, Second Military Medical University, Shanghai, China

    Chunquan Sheng

  2. College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA

    Gunda I. Georg

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Zhang, Y., Wang, W. (2018). Small-Molecule Inhibitors for the β-Catenin/T Cell Factor Protein-Protein Interaction. In: Sheng, C., Georg, G. (eds) Targeting Protein-Protein Interactions by Small Molecules. Springer, Singapore. https://doi.org/10.1007/978-981-13-0773-7_9

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