ONO-8711 dicyclohexylamine is a selective and orally active EP1 competitive antagonist with Ki value of 0.6 nM and 1.7 nM for human and mouse EP1 respectively. ONO-8711 dicyclohexylamine effectively reduces tumor incidence and multiplicity in mouse models of colon, breast, and oral cancer[1].
ONO-8711 (10 and 30 μM; 30 min) blocks the contractions induced by sulprostone in human pulmonary veins in a non-competitive manner[2].
ONO-8711 inhibits PGE2-induced increase in cytosolic Ca2+ concentration with IC50s of 0.21 μM, 0.05 μM, and 0.22 μM for the mouse, human, and rat receptors, respectively[3].
ONO-8711 (400 or 800 p.p.m.; p.o.; for 20 weeks) suppresses cancer incidence and delays occurrence of breast tumors[3].
| Animal Model: | Female Sprague-Dawley rats (induced breast cancer by gavage of 85 mg/kg PhIP 4 times for 2 weeks) |
| Dosage: | 400 or 800 p.p.m. |
| Administration: | p.o.; for 20 weeks |
| Result: | Did not induce any symptoms of toxicity at 800 p.p.m.. Delayed occurrence of breast tumors for 2 or 4 weeks at 400 or 800 p.p.m., respectively. Significantly suppressed cancer incidence compared with the control diet group at 800 p.p.m. (56% versus 79%, P < 0.05). |
[1]. Watanabe K, et al. Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis. Cancer Res. 1999 Oct 15;59(20):5093-6.
[2]. Norel X, et al. Vasoconstriction induced by activation of EP1 and EP3 receptors in human lung: effects of ONO-AE-248, ONO-DI-004, ONO-8711 or ONO-8713. Prostaglandins Other Lipid Mediat. 2004 Oct;74(1-4):101-12.
[3]. Kawamori T, et al. Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP(1) antagonist, on breast cancer development. Carcinogenesis. 2001 Dec;22(12):2001-4.