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Updated: Jan 12, 2026

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使用异质模组体对β-catenin/B细胞淋巴瘤9的蛋白相互作用的破坏

Peng Sang^1,2,3, Jiacheng Wei⁴, Mingshuang Wu¹

¹State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, School of Pharmaceutical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Journal of the American Chemical Society

|November 3, 2025

概括

通过破坏β-catenin和BCL9的相互作用来抑制Wnt/β-catenin信号传递. 通过减少细胞增殖和改善血清稳定性,这些化合物具有结直肠癌治疗潜力.

科学领域:

医学化学
分子生物学
癌症研究

背景情况:

异常的Wnt/β-catenin信号驱动着结直肠癌和其他恶性瘤.
抑制这种途径是开发新型抗瘤药物的关键策略.

研究的目的:

设计和合成新的螺旋式1:1α/硫-γ-AA抑制剂.
破坏β-catenin和BCL9之间的蛋白质-蛋白质相互作用 (PPI).

主要方法:

的合成和表征.
循环二重化光谱和分子建模.
在体外测试评估细胞透性,基因表达,PPI破坏和细胞增殖.

主要成果:

合成的1:1型α/sulfonyl-γ-AA模仿BCL9侧链,并与纳米分子亲和力结合β-catenin.
化合物表现出优异的细胞透性,降低Wnt目标基因的调节,并破坏β-catenin/BCL9 PPI.
观察到Wnt过活的CRC细胞系的增殖显著减少,同时增加了血清稳定性.

结论:

新型混合模剂有效抑制Wnt/β-catenin信号传递和CRC细胞增殖.
由于细胞透和血清稳定性,这些化合物具有治疗潜力.
这项研究提出了调节蛋白与蛋白相互作用的新策略.

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