DuP-697

DuP-697 is a member of the vicinal diaryl heterocycles and a potent, irreversible, selective and orally active COX-2 inhibitor (IC₅₀ of 10 nM and 800 nM for human COX-2 and COX-1, respectively). DuP-697 exerts antiproliferative (IC₅₀ of 42.8 nM), antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. DuP-697 inhibits prostaglandin synthesis and has anti-inflammatory, anticancer and antipyretic effects^[1][2][3]. In Vitro: DuP-697 (0-100 nM; 24 hours; HT29 cells) treatment shows antiproliferative with an IC₅₀ value of 42.8 nM^[1].
DuP-697 (25-100 nM; 72 hours; HT29 cells) treatment causes concentration dependent apoptosis in HT29 cells. The percentage of UR (apoptosis portion) area increases gradually according to the concentration of DuP-697 from 7% in control group to 52% in 100 nM DuP-697^[1].
DuP-697 in 100, 10 and 1 nM concentrations cause antiangiogenic effect. Antiangiogenic scores of DuP-697 are 1.2, 0.8 and 0.5, respectively^[1]. In Vivo: DuP-697 is a potent inhibitor of paw swelling in nonestablished and established adjuvant arthritis in rats (ED₅₀ = 0.03 and 0.18 mg/kg/day, respectively). DuP-697 has no effect on phenylquinone writhing in rats (ED₅₀ greater than 100 mg/kg), but is analgetic against inflammation-related pain in the Randall-Selitto assay (ED₅₀ = 3.5 mg/kg) and is a very potent antipyretic agent (ED₅₀ = 0.05 mg/kg). DuP-697 (5 mg/kg i.v.) does not alter renal blood flow or the renal vascular response to angiotensin II in furosemide-pretreated, volume-depleted rats^[2].
DuP-697 is a moderate inhibitor of bull seminal vesicle prostaglandin (PG) synthesis (IC₅₀ of 24 μM) and a potent inhibitor of rat brain PG synthesis (IC₅₀ of 4.5 μM) but was ineffective against rat kidney PG synthesis (IC₅₀ of 75 μM)^[2].