ONO-AE3-208

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Background

ONO-AE3-208 is an antagonist of EP4 [1].
EP4 is one of the prostaglandin E2 receptors and is associated with inflammatory disease and cancer such as prostate cancer. As an antagonist of EP4, ONO-AE3-208 is expected to be a potential therapy for prostate cancer. In vitro assays show that ONO-AE3-208 can suppress the migration and invasion of prostate cancer cells. 10μM of ONO-AE3-208 decreases wound healing proportion of PC3 and LNCaP cell lines in wound-healing assay. And in Transwell Invasion assay, ONO-AE3-208 inhibits cell invasion even at concentration of 0.1μM. ONO-AE3-208 is also reported to suppress bone metastasis in vivo [1].
Since activation of E2 can increase the expression of matrix metalloproteinase (MMP) and release inflammatory cytokines, and then exacerbates abdominal aortic aneurism (AAA) formation, ONO-AE3-208 is also used in the studies of AAA formation. It has been proved that ONO-AE3-208 can cause the elastic fiber degradation and inhibit AAA formation in vivo in a dose-dependent manner [2].

[1] Song Xu, Zhengyu Zhang, Osamu Ogawa,Takeshi Yoshikawa, Hiromasa Sakamoto, Noboru Shibasaki, akayuki Goto, Liming Wang, Naoki Terada. An EP4 antagonist ONO-AE3-208 suppresses cell invasion, migration and metastasis of prostate cancer. Cell Biochem Biophys. 2014, April.
[2] Utako Yokoyama, Ryo Ishiwata, Mei-Hua Jin, Yuko Kato, Orie Suzuki, Huiling Jin, Yasuhiro Ichikawa, Syun Kumagaya, Yuzo Katayama, Takayuki Fujita, Satoshi Okumura, Motohiko Sato, Yukihiko Sugimoto, Hiroki Aoki, Shinichi Suzuki, Munetaka Masuda, Susumu Minamisawa, Yoshihiro Ishikawa. Inhibition of EP4 Signaling Attenuates Aortic Aneurysm Formation. Plos One. 2012, May. 7, 5, e36724.