Wnt signaling proteins are small secreted proteins that are active in embryonic development, tissue homeostasis, and tumorigenesis. Wnt proteins initiate cell signaling by binding Frizzled (Fz) receptors, a family of G protein-coupled receptors. FzM1 is an allosteric ligand of Fz4. At 10 ?M, it inhibits nuclear translocation of β-catenin in U87MG glioma cells treated with lithium chloride, a GSK3 inhibitor that enhances the Wnt canonical signaling pathway. FzM1 impairs the ability of U87MG cells to form neurospheres in culture and stimulates the differentiation of Caco-2 epithelial colorectal adenocarcinoma cells.