TABLE 9

Potential therapeutic application of EP4 agonists

AgonistRouteDoseSpeciesExperimental ModelIndicationReference
3,7-Dithia PGE1 and its isopropyl esterTopical0.01–0.1%Monkey“Glaucomatous” monkey intraocular pressureGlaucomaWoodward et al., 2009
4819-CDSubcutaneous0.3 mg/kgMouseIschemia-reperfusion injuryMyocardial infarctionXiao et al., 2004
AEI-734ColitisKabashima et al., 2002
AGN 205203 and its methyl esterSubcutaneous3 mg/kgMouseDextran sodium sulfate colitisColitisJiang et al., 2007
CP-734432Subcutaneous0.3–3 mg/kgRatOvariectomized ratsOsteoporosisKe et al., 2006
ONO-4819Subcutaneous10, 30 μg/kgRatFemoral drill-hole injuryBone fracture healing, osteoporosisTanaka et al., 2004
ONO-4819Subcutaneous3, 30 μg/kgRatMechanical loading, to tibiaBone fracture, osteoporosisHagino et al., 2005
ONO-4819Intravenous100 ng/kgRatOvariectomized ratOsteoporosisYoshida et al., 2002
ONO-AE1-329Intracolonic25, 100 μg/kgRatDextran sodium sulfate colitisColitisNitta et al., 2002
ONO-AE1-329Intravenous1–10 μg/kgRatIndomethacin-induced lesionsNSAID-induced gastrointestinal lesionsKunikata et al., 2002
ONO-AE1-329Intraperitoneal0.1 mg/kgRatIndomethacin-induced lesionsNSAID-induced gastrointestinal lesionsHatazawa et al., 2006
ONO-AE1-329Subcutaneous0.1–1000 ng/gRatNeonatal ductus arteriosus dilatationPremature birthMomma et al., 2005
ONO-AE1-329Local gelatin plug1 mg/mlGuinea pigAuditory brain stem responseSensorineural hearing lossHori et al., 2009
ONO-AE1-329Subcutaneous0.05, 0.5 mg/kg 55 μg daily infusion per animalMouseN2 receptor knockout miceNephrogenic diabetes insipidusLi et al., 2009
ONO-AE1-329Subcutaneous100 μg/kgMouseAnti-glomerular basement membrane antibody nephritisGlomerulonephritisNagamatsu et al., 2006
ONO-AE1-329Intravenous1–10 μg/kgRatEndotoxinSepticemiaSakamoto et al., 2004
PF-04475270Topical0.002–0.1 mg/mlDogNormal dog intraocular pressureGlaucomaPrasanna et al., 2009