“…The discrepancy between these results and those found in the cell-based assay could be due to a different inhibitor sensitivity exhibited by the mouse and human COX isozymes, as already reported for other anti-inflammatory compounds. 10 As a matter of the fact, such a dramatic loss in COX inhibitory potency and a drop in selectivity under the HWB assay conditions are common to other selective COX-2 inhibitors, such as valdecoxib, 31,32 etoricoxib, 31,32 lumiracoxib, 33 and rofecoxib, 34,35 as well as tNSAIDs such as nimesulide 16,31 and meloxicam. 36,37 It should be pointed out that, according to the test, 10a, 10c, and 11c exhibited an affinity for COX-2 5-10-fold higher than that for COX-1, which should translate clinically into an acceptable GI safety, and allowing for a sufficient prostacyclin generation that should mitigate the CV effects showed by overly selective COX-2 inhibitors, as previously discussed.…”