Because we observed the promising molecular efficacy of DDQ-1 with even more potent activity against DCLK1 kinase activity, and therapeutic efficacy against CRC stemness via the XRCC5/COX2 signaling axis, further investigations using DDQ-1 and its derivatives may be highly informative for identifying and optimizing a better pharmacophore for DCLK1 inhibition. Here, PTGS2 is linked to colorectal carcinoma.