Biophysical Survey of Small-Molecule β-Catenin Inhibitors: A Cautionary Tale.

ABSTRACT: The canonical Wingless-related integration site signaling pathway plays a critical role in human physiology, and its dysregulation can lead to an array of diseases. β-Catenin is a multifunctional protein within this pathway and an attractive yet challenging therapeutic target, most notably in oncology. This has stimulated the search for potent small-molecule inhibitors binding directly to the β-catenin surface to inhibit its protein-protein interactions and downstream signaling. Here, we provide an account of the claimed (and some putative) small-molecule ligands of β-catenin from the literature. Through in silico analysis, we show that most of these molecules contain promiscuous chemical substructures notorious for interfering with screening assays. Finally, and in line with this analysis

SUBMITTER: McCoy MA 

PROVIDER: S-EPMC9150122 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature