Cyclooxygenase (COX), also called prostaglandin endoperoxide synthase, is an oxidoreductase enzyme, including two isoforms: COX-I and COX-II. It acts in the formation of biological modulators such as prostaglandins (PGs), prostacylins, and thromboxane from arachidonic acid. COX-I is present in all tissues and is more associated with PG production in gastric mucosa and thromboxane production in platelets. COX-II expresses up-regulated in response to inflammatory stimuli and elevates prostaglandin levels, thus taking part in the inflammatory response. Therefore, COX is a common target for anti-inflammation. And the discovery of COX inhibitors can become useful agents for relieving pain and inflammation.

Loxoprofen is an orally active, non-steroidal, and non-selective COX inhibitor.

Loxoprofen, also an anti-inflammatory prodrug (NSAID), has inhibitory activity against COX with IC50s of 6.5 μM and 13.5 μM for COX-I and COX-II, respectively. It has antipyretic and analgesic activity to relieve pain and inflammation caused by chronic and transitory conditions. Cytochrome P450 (CYP) can convert this agent into an inactive hydroxylated metabolite (OH-LOXs).

The formation of atherosclerotic lesions is related to inflammation. In apoE-/- mice, Loxoprofen (4 mg/kg/day; PO, for 56 days) inhibits platelet aggregation and significantly reduces the extent of atherosclerotic lesion area of the aortic root to 41.5% after administration for 7 days, and 75.6% for 56 days. Moreover, serum levels of total cholesterol, triglycerides, or free fatty acids do not show to be affected.

Besides, Loxoprofen (60 μg/mL/day; PO, for 24 days) suppresses tumor growth and angiogenesis in LLC-implanted C57BL/6 mice and KLN205-implanted BDF1 mice. Loxoprofen as well as suppresses the expression of VEGF in mice with LLC tumors, and inhibits the tubular formation of HUVECs. In addition, 50 mg/ml LOX significantly reduces the concentration of PGE2 in the supernatant of cultured LLC cells.

In conclusion, Loxoprofen is an orally active, non-steroidal, and non-selective COX inhibitor, with antipyretic, analgesic, and antitumor activity.



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