ONO-8711

ONO-8711 is a novel and selective EP1 antagonist.

Prostaglandin (PG) E2 functions by acting on a group of G-protein-coupled receptors (GPCRs) EP receptros. The EP receptors exhibit differences in signal transduction, tissue localization, and regulation of expression. The EP receptors have been implicated in various physiological and pathophysiological functions [2].

In vitro: In human pulmonary vessels, ONO-8711 (30 μM) non-competitively blocked the contractions produced with sulprostone, an EP1,3 agonist [3].

In vivo: In azoxymethane-treated C57BL/6J mice, administration of 250, 500, or 1000 ppm of ONO-8711 dose-dependently reduced ACF formation. In Min mice with a nonsense mutation in the adenomatous polyposis coli gene, treatment with 500 ppm ONO-8711 significantly reduced the number of intestinal polyps [1]. In female SD rats given PhIP, administration of ONO-8711 at 400 or 800 p.p.m. delayed occurrence of breast tumors for 2 or 4 weeks, respectively [4]. Treatment with ONO-8711 (800 p.p.m.) significantly decreased PhIP-induced breast cancer incidence, multiplicity and volume when compared with those of control rats [4].

References:
[1] Watanabe K, Kawamori T, Nakatsugi S, et al.  Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis[J]. Cancer research, 1999, 59(20): 5093-5096.
[2] Sugimoto Y, Narumiya S.  Prostaglandin E receptors[J]. Journal of Biological Chemistry, 2007, 282(16): 11613-11617.
[3] Norel X, de Montpreville V, Brink C.  Vasoconstriction induced by activation of EP 1 and EP 3 receptors in human lung: effects of ONO-AE-248, ONO-DI-004, ONO-8711 or ONO-8713[J]. Prostaglandins & other lipid mediators, 2004, 74(1): 101-112.
[4] Kawamori T, Uchiya N, Nakatsugi S, et al.  Chemopreventive effects of ONO-8711, a selective prostaglandin E receptor EP1 antagonist, on breast cancer development[J]. Carcinogenesis, 2001, 22(12).