ONO-AE3-208 is an EP4 antagonist, and suppresses cell invasion, migration, and metastasis of prostate cancer. The in vivo bone metastasis of PC3 was also suppressed by ONO-AE3-208 treatment[3]. Hypoxia-enhanced functions in miRNA-high cells are inhibited by COX-2 inhibitor (Celecoxib), EP4 antagonist (ONO-AE3-208), and irreversible PI3K/Akt inhibitor (Wortmannin)[4]. EP4 antagonism (ONO AE3-208) improves the NTS (nephrotoxic serum nephritis) phenotype, probably by decreasing mainly Cxcl-5 production in tubular cells, thereby reducing renal neutrophil infiltration[5]. Intravesical application of ONO-AE3-208 (30 μm), but not vehicle application, significantly increased ICIs (intercontraction intervals) in rats with prostatic inflammation, whereas ONO-AE3-208 at this concentration did not significantly affect any cystometric values in control rats[6].
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