生物活性

• 描述Metabolism of free arachidonic acid (AA), liberated by phospholipase A2 enzymes, leads to the formation of prostanoids and leukotrienes (LTs) that are considered as potent mediators of inflammatory reactions. Whereas the cyclooxygenases (COXs)-1 and -2 catalyse the initial steps in the biosynthesis of prostanoids, 5-lipoxygenase (5-LOX) is the key enzyme in the generation of LTs. Licofelone (ML-3000) is a dual inhibitor of and cyclooxygenase being considered as a treatment for osteoarthritis. Dog model of osteoarthritis was orally administered with Licofelone twice daily with food, at a total daily dose of 2.5 mg/kg or 5.0 mg/kg for 8 weeks. It was found that Licofelone treatment markedly reduced the level of chondrocyte apoptosis to the same extent in both therapeutic groups, the levels of caspase-3, COX-2, and iNOS in cartilage from both condyles and plateaus were also significantly decreased, compared to the placebo group. Licofelone at 195 nM to 50 µM for 72 h reversed the stem-like properties of ovarian multicellular tumor spheroids (MCTS). Importantly, the combination of licofelone (50 mg/kg) with paclitaxel (12 mg/kg) prolonged the median survival of ovarian cancer PDX (patient-derived tumor xenograft) mice model (>141 days) relative to paclitaxel (115 days), licofelone (37 days), or vehicle (30 days).