6CEPN is identified as a novel selective COX-1 inhibitor. A, chemical structure of 6CEPN. B, proposed molecular model of 6CEPN binding with COX-1. 6CEPN binds to the active site of COX-1 by forming 3 hydrogen bonds with Tyr355, Phe518 and Ser530. C, proposed molecular model of 6CEPN binding with COX-2. 6CEPN failed to occupy the active pocket of COX-2 (left panel) but might bind to COX-2 in another region (i.e., His207 and His388). D, 6CEPN binds with COX-1 and COX-2 in vitro. A pull-down assay was performed using recombinant COX-1 and COX-2 proteins. Proteins bound to the beads were analyzed by Western blotting. E, 6CEPN specifically inhibits COX-1 activity in vitro. The inhibitory activity of 6CEPN was evaluated using a COX Inhibitor Screening Kit (Cayman) according to the manufacturer’s instructions. Data are presented as means ± S.E.M. (n = 4). The asterisks (***) indicate a significant (p < 0.001) difference compared to each respective control group.