生物活性

• 描述Rofecoxib is a potent and orally active inhibitor of COX-2, with IC50s of 26 and 18 nM for human COX-2 in human osteosarcoma cells and Chinese hamster ovary cells, with a 1000-fold selectivity for COX-2 over COX-1 (IC50 >50 μM in U937 cells and >15 μM in Chinese hamster ovary cells). Rofecoxib time dependently inhibits purified human recombinant COX-2 (IC50 = 0.34 μM) but suppresses purified human COX-1 in a non-time-dependent manner that can only be observed at a very low substrate concentration (IC50 = 26 μM at 0.1 μM arachidonic acid concentration). Rofecoxib selectively inhibits lipopolysaccharide-induced, COX-2-derived PGE(2) synthesis with an IC50 value of 0.53 ± 0.02 μM compared with an IC50 value of 18.8 ± 0.9 μM for the inhibition of COX-1-derived thromboxane B(2) synthesis after blood coagulation. Rofecoxib potently inhibits carrageenan-induced paw edema (ID50 = 1.5 mg/kg), carrageenan-induced paw hyperalgesia (ID50=1.0 mg/kg), lipopolysaccharide-induced pyresis (ID50 = 0.24 mg/kg), and adjuvant-induced arthritis (ID50 = 0.74 mg/kg/day) in rodent models. Rofecoxib also protects adjuvant-induced destruction of cartilage and bone structures in rats^[3]. Rofecoxib attenuated retinal angiogenesis by inhibiting the expression of COX-2 (cyclooxygenase-2) and VEGF (vascular endothelial growth factor) mRNA and protein^[4]. Rofecoxib (36 μM) causes a cell proliferation of 68% in MPP89, of 58% in Ist-Mes-1 and 40% in Ist-Mes-2. MSTO-211H and NCI-H2452 treated with 36 μM of Rofecoxib have a survival of 97% and 90% respectively. Rofecoxib (36 μM) decreases COX-2 and mRNA levels in Ist-Mes-1, Ist-Mes-2 and MPP89 cell lines^[5].