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Recent advances in β-catenin/BCL9 protein–protein interaction inhibitors

    Hao Zhang‡

    Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China

    School of Pharmacy, Fudan University, Shanghai, 201203, China

    ‡Authors contributed equally

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    ,
    Ya Bao‡

    Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China

    School of Chemistry & Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China

    ‡Authors contributed equally

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    ,
    Chenglong Liu‡

    School of Pharmacy, Fudan University, Shanghai, 201203, China

    ‡Authors contributed equally

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    ,
    Jianqi Li§

    ***Author for correspondence:

    E-mail Address: lijianqb@126.com

    Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China

    §Authors share senior co-authorship

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    ,
    Di Zhu§

    **Author for correspondence:

    E-mail Address: zhudi@fudan.edu.cn

    School of Pharmacy, Fudan University, Shanghai, 201203, China

    §Authors share senior co-authorship

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    &
    Qingwei Zhang§

    *Author for correspondence:

    E-mail Address: sipiqingwei@163.com

    Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China

    §Authors share senior co-authorship

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    Published Online:https://doi.org/10.4155/fmc-2020-0357

    Wnt/β-catenin signaling is crucial both in normal embryonic development and throughout the life of an organism. Moreover, aberrant Wnt signaling has been associated with various diseases, especially cancer and fibrosis. Recent research suggests that direct targeting of the β-catenin/BCL9 protein–protein interaction (PPI) is a promising strategy to block the Wnt pathway. Progress in understanding the cocrystalline complex and mechanism of action of the β-catenin/BCL9 interaction facilitates the discovery process of its inhibitors, but only a few inhibitors have been reported. In this review, the discovery and development of β-catenin/BCL9 PPI inhibitors in the areas of drug design, structure–activity relationships and biological and biochemical properties are summarized. In addition, perspectives for the future development of β-catenin/BCL9 PPI inhibitors are explored.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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