Indole-2-amide based biochemical antagonist of Dishevelled PDZ domain interaction down-regulates Dishevelled-driven Tcf transcriptional activity

We designed and synthesized a series of indole-2-amide-based compounds that antagonize interaction between the Dishevelled (Dvl) PDZ domain and a peptide derived from the natural PDZ ligand Frizzled-7 (Fz7). These compounds inhibit Tcf-mediated transcription activated by exogenous Dvl via the biochemical antagonism. We confirmed tumor cell-selective activation of caspases by these compounds.