Discovery of dual agonist for Prostaglandin E₂, ONO-8055

Abstract

Our purpose is to develop PGE₂ analogs possessing highly potent dual agonist activity with selectivity for EP₂ and EP₃ over the other two subtypes (EP₁ and EP₄), because a dual EP₂ and EP₃ agonist is expected as an effective therapeutics addressing unmet medical needs for treatment of underactive bladder (UAB). The resulting compound, ONO-8055, showed excellent potency, subtype selectivity and good pharmacokinetic profiles. Regarding in vivo efficacy, ONO-8055 improved the lower urinary tract dysfunctions of neurogenic underactive bladder in a rat lumbar spinal stenosis (LCS) model. Furthermore, as a result of Phase I trial in Europe, there is no concern over safety and PK.