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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 21, 2021
- Source ID
- 10.1002/med.21787
Entities
People
- Haitao (mark) Ji
- Zhen Wang
- Zilu Li
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- Susan G. Komen for the Cure
- United States Department of Defense
- University of South Florida