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Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives.

ABSTRACT: 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.

SUBMITTER: Wang Z

PROVIDER: S-EPMC8217106 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Direct targeting of β-catenin in the Wnt signaling pathway: Current progress and perspectives.

Wang Zhen Z Li Zilu Z Ji Haitao H

Medicinal research reviews 20210121 4

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 sup ...[more]

PMID: 33475177

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