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Among many signal pathways, the aberrant activation of Wnt/β-catenin signal is the most important for the occurrence and development of various cancer.179 More than 80% of cancer patients have inactivating mutations of APC or activating mutations of CTNNB1, leading to the messenger molecule β-catenin protein continuing to accumulate in cells, which eventually leads to the excessive activation of Wnt/β-catenin signal and the proliferation of cancer cells.180 As β-catenin is the central player of the canonical Wnt/β-catenin signaling and is frequently mutated in cancers, it is the most attractive target for cancer therapy.181 However, β-catenin has no enzymatic activity and small-molecule binding pockets, and has a large interaction interface with other proteins. Therefore, it is difficult for such small molecule inhibitors to completely inhibit the function of β-catenin.182 Thus, inducing the degradation of β-catenin is an ideal method for treating Wnt/β-catenin signal-related diseases.
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