The WNT/beta-catenin pathway regulates a huge number of cellular functions, and its dysregulation is correlated to the development of cancer. In this work, we focused on the interaction between Dishevelled 1 (DVL1) protein, an important player in this pathway, and its cognate receptor Frizzled via a shared PDZ domain. Computational studies led to the discovery of racemate RS4690 (1) showing selective inhibition of DVL1 binding. After separation of the racemic mixture, enantiomer (S)-1 inhibited DVL1 with an EC50 of 0.49 microM and the growth of HCT116 cells that did not present the APC mutation with an EC50 value 7.1 microM, and caused a high level of ROS production. Compound (S)-1 shows potential as a new therapeutic agent against WNT-dependent colon cancer.