In this study, the activities of 3 DIM-3,5 analogs and their effect on NR4A1 and NR4A2 as dual NR4A1/NR4A2 ligands were investigated, and we show that like NR4A1, NR4A2 exhibits pro-oncogenic activity in colon cancer cells, and the compounds act as dual-receptor inverse agonists that inhibit NR4A1-/NR4A2-regulated responses. This evidence concerns the gene NR4A2 and colonic neoplasm.