Fenoprofen calcium hydrate

Fenoprofen is a more potent inhibitor of collagen-induced platelet aggregation than either aspirin or phenylbutazone. ^[1] Fenoprofen inhibits the formation of palmitoyl-CoA in both microsomal and peroxisomal fractions, and inhibits the beta-oxidation of lignoceric acid and cerotic acid in rat hepatocytes. ^[5] Fenoprofen exhibits modest antiproliferative activity against HT-29, DID-1, and SW480 cells with IC50 of 240 μM, 300 μM, and 360 μM, respectively. ^[6] Fenoprofen (0.1 mM) is an efficient activator of peroxisome proliferator-activated receptor gamma (PPARγ), activating the receptor to a degree comparable to that obtained with the PPARγ ligands BRL49653 and 15-deoxy-D^12,14-PGJ₂ and the peroxisome proliferator Wy14643. Fenoprofen is also an efficacious activator of PPARα, activating the receptor to a degree comparable to that obtained with the strong peroxisome proliferator Wy14643. Consistently, Fenoprofen treatment promotes lipogenesis in C3H10T1/2 cells. ^[7] Although Fenoprofen displays only modest antiproliferative activity, Fenoprofen amides can potently induce cell cycle arrest at the G1 phase, as well as apoptosis, probably because of a greater lipophilicity and/or better cell uptake. ^[9]

Oral administration of Fenoprofen at 50 mg/kg potently inhibits thrombus formation by 47%, whereas a dose of 200 mg/kg of aspirin is required to reduce thrombus formation 21 %. ^[1] Similar to indomethacin, adminstration of Fenoprofen inhibits prostaglandin synthesis. ^[2] In rats with type II collagen-induced arthritis, Fenoprofen treatment at 40 mg/kg/day partially suppresses the paw swelling, but has no significant effect on humoral and cellular responses. ^[3] Administration of Fenoprofen depresses the rebound contraction, thus transforming the brisk relaxant response, elicited by vagal stimulation or ATP, into long-lasting relaxation. ^[4] Administration of Fenoprofen causes a strong and dose-related induction of peroxisomal palmitoyl-CoA oxidase, and of carnitine acyltransferase and acyl-CoA hydrolase activities in liver homogenates of mice fed diets. Hepatic catalase activity is significantly increased in mice fed the diet with 0.05 and 0.1% fenoprofen but not the 1% fenoprofen-containing diet. ^[8]

Cells are exposed to various concentrations of Fenoprofen for 6 days. Cell number is determined using the SRB colonimetnic protein stain assay. After 6 days of culture, cells are fixed by the addition of cold trichloroacetic acid to a final concentration of 10%. Plates are incubated at 4 °C for 1 hour, then the supernatant is aspirated and the plates are washed with deionized water. SRB solution is formulated to 0.4% w/v in 1% acetic acid; 100 μL is added to each well and the plates are incubated for 10 minutes at room temperature. Unbound SRB is removed by washing with 1% acetic acid followed by air drying. Bound stain is solubilized with 50 mM unbuffered Tris and absorbance is read by an automated spectrophotometer at a single wavelength of 540 nm.

• [1] Herrmann RG, et al. Proc Soc Exp Biol Med, 1972, 139(2), 548-552.
• [2] Patrono C, et al. Pharmacol Res Commun, 1974, 6(5), 509-518.
• [3] Phadke K, et al. Clin Exp Immunol, 1982, 47(3), 579-586.

• [4] Baccari MC, et al. Exp Physiol, 1990, 75(3), 415-418.
• [5] Lageweg W, et al. Biochem Pharmacol, 1993, 46(1), 79-85.
• [6] Hixson LJ, et al. Cancer Epidemiol Biomarkers Prev, 1994, 3(5), 433-438.

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