Discovery of Novel 3-Phenylpiperidine Derivatives Targeting the β-Catenin/B-Cell Lymphoma 9 Interaction as a Single Agent and in Combination with the Anti-PD-1 Antibody for the Treatment of Colorectal Cancer
Abstract:Direct disruption of the β-catenin/B-cell lymphoma 9 (BCL9) protein−protein interaction (PPI) is a potential strategy for colorectal cancer (CRC) treatment through inhibiting oncogenic Wnt activity. Herein, a series of 3-phenylpiperidine derivatives were synthesized and evaluated as β-catenin/BCL9 PPI inhibitors. Among them, compound 41 showed the best IC 50 (0.72 μM) in a competitive fluorescence polarization assay and a K D value of 0.26 μM for the β-catenin protein. This compound selectively inhibited the g… Show more
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