Challenging Reported Frizzled-Targeting Compounds in Selective Assays Reveals Lack of Functional Inhibition and Claimed Profiles.

ABSTRACT: Selective inhibitors of Frizzled (FZD) GPCRs are highly sought after as potentially highly efficacious and safe treatments for cancer as well as tools in regenerative medicine and fundamental science. In recent years, there have been several reports claiming the identification of small molecule agents that are selective toward certain FZD proteins using a variety of approaches. However, the majority of these studies lacked a selective functional assay to validate their functionality. In this study, we describe the development and application of a selective assay for individual FZD proteins. Our findings indicate that the majority of reported compounds lack the capacity to inhibit the functioning of the claimed FZD proteins when stimulated by a Wnt ligand in the canonical pathway. Instead,

SUBMITTER: Koval A 

PROVIDER: S-EPMC11650735 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature