Rofecoxib

A potent, selective and orally active COX-2 inhibitor with IC50 of 26 nM for inhibition of the COX-2-dependent production of PGE2 in human osteosarcoma cells; displays 1,000-fold selectivity over COX-1 activity; selectively inhibits LPS-induced, COX-2-derived PGE (2) synthesis after blood coagulation (IC50=0.53 uM) ; exhibits anti-inflammation activity in osteoarthritis and rheumatoid arthritis rodent models.Pain Withdrawn (In Vitro) :Rofecoxib (MK-0966) is a potent and orally active inhibitor of COX-2, with IC50s of 26 and 18 nM for human COX-2 in human osteosarcoma cells and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 (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. (In Vivo) :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. In a 51Cr excretion assay for detection of gastrointestinal integrity in either rats or squirrel monkeys, rofecoxib shows no effect at doses up to 200 mg/kg/day for 5 days. Rofecoxib (15 mg/kg, i.p.) reduces the blood vessels attached to the internal limiting membrane (ILM) in mice. COX-2 and VEGF protein expressions, COX-2 mRNA and VEGF mRNA are also significantly decreased by Rofecoxib in ROP mice.

162011-90-7

MK-0996 | MK-966

Pharmacology & Drug Discovery

>98% (HPLC)

10 mM in DMSO

O=C1C (C2=CC=CC=C2) =C (C3=CC=C (S (=O) (C) =O) C=C3) CO1

C17H14O4S

314.3557

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.