COX-2 is the more important source of prostanoid formation in inflammation and in proliferative diseases. In particular, COX-2 prefers prostaglandin I synthase and the microsomal PGES isozymes. DuP-697 is an irreversible selective inhibitor of COX-2.
DuP-697 exerts antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect, the half-maximum inhibition concentration (IC50) is 42.8 nM. Antiangiogenic scores are 1.2, 0.8 and 0.5 for 100, 10 and 1 nM DuP-697 concentrations, respectively. DuP-697 demonstrates a potent action in inhibiting HT29 cell growth and inducing apoptosis and antiangiogenic effect.
Dup-697 selectively inhibits human COX-2, with significantly less ability to inhibit COX-1. This is consistent with its anti-inflammatory activity in rats without gastric toxicity. Especially, DuP-697 is an orally effective prostaglandin synthesis inhibitor. 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). In addition, DuP-697 is analgetic against inflammation-related pain in the Randall-Selitto assay (ED30= 3.5 mg/kg) and is a very potent antipyretic agent (ED50=0.05 mg/kg).
DuP-697 is a moderate inhibitor of bull seminal vesicle prostaglandin (PG) synthesis (IC50 24 μM). Moreover, DuP-697 is a potent inhibitor of rat brain PG synthesis (IC50=4.5 μM) but is ineffective against rat kidney PG synthesis (IC50 75 μM). Furthermore, DuP-697 shows high potency as an anti-inflammatory and antipyretic agent and its minimal toxicity profile.
In conclusion, DuP-697 is a selective COX-2 inhibitor that has antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. DuP-697 may be a promising agent in the treatment of colorectal cancer. Anti-inflammatory drug as an anticancer agent.
Gans KR, et al. Anti-inflammatory and safety profile of DuP 697, a novel orally effective prostaglandin synthesis inhibitor. J Pharmacol Exp Ther. 1990 Jul;254(1):180-7.