 Abstract we designed and synthesized novel quinozolinone tethered phenyl urea derivatives, 6A, P, that triple target the double mutant EGFRL858R, T790M, COX-2, and LOX. Compounds, 6E, 6D, 6J, 6M, and 6N, not only had low micromolar IC50 inhibitory activities against the three targets, but they also showed good selectivity for COX-2 over COX-1, and for EGFRL858R, T790M over wild type EGFR. Except for 6E and 6N, all of the tested compounds inhibited the NO production significantly more potently than Selexa, Declophinac, and Indomaphacin. Compounds 6I and 6K reduced ROS levels more effectively than Selexa and Declophinac. In terms of inhibiting TNF production, 6O treated cells showed TNF level, which is 1-0 times lower than Selexa. Furthermore, 6. This article was authored by HENDKOTUYA, SAMARESK, ARMEDSUPDELKULEK, and others. We are article.tv, links in the description below.