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Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives
Medicinal Research Reviews ( IF 13.3 ) Pub Date : 2021-01-21 , DOI: 10.1002/med.21787
Zhen Wang 1 , Zilu Li 2 , Haitao Ji 1, 2
Affiliation  

Aberrant activation of the Wnt/β-catenin signaling circuit is associated with cancer recurrence and relapse, cancer invasion and metastasis, and cancer immune evasion. Direct targeting of β-catenin, the central hub in this signaling pathway, is a promising strategy to suppress the hyperactive β-catenin signaling but has proven to be highly challenging. Substantial efforts have been made to discover compounds that bind with β-catenin, block β-catenin-mediated protein–protein interactions, and suppress β-catenin signaling. Herein, we characterize potential small-molecule binding sites in β-catenin, summarize bioactive small molecules that directly target β-catenin, and review structure-based inhibitor optimization, structure–activity relationship, and biological activities of reported inhibitors. This knowledge will benefit future inhibitor development and β-catenin-related drug discovery.

中文翻译:

Wnt信号通路中β-连环蛋白的直接靶向:当前进展和展望

Wnt/ β-连环蛋白信号通路的异常激活与癌症复发和复发、癌症侵袭和转移以及癌症免疫逃避有关。直接靶向β-连环蛋白(该信号通路的中心枢纽)是抑制过度活跃的β-连环蛋白信号传导的有前景的策略,但已被证明具有高度挑战性。已经做出了大量努力来发现与β-连环蛋白结合、阻断β-连环蛋白介导的蛋白质-蛋白质相互作用和抑制β-连环蛋白信号传导的化合物。在此,我们描述了β -catenin中潜在的小分子结合位点,总结了直接靶向的生物活性小分子β-连环蛋白,并回顾了基于结构的抑制剂优化、构效关系和已报道抑制剂的生物活性。这些知识将有利于未来的抑制剂开发和β-连环蛋白相关药物的发现。
更新日期:2021-01-21
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