IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys

Investigative Ophthalmology & Visual Science
Shinsaku YamaneKazuhito Kawabata

Abstract

The purpose of this study was to determine whether a better IOP reduction can be observed in conscious, normotensive monkeys treated with ONO-9054, a novel dual EP3 and FP receptor agonist, compared with prostaglandin F2α analogs. The binding affinities and agonistic activities of ONO-AG-367, a carboxylic acid of ONO-9054, to prostanoid receptors were assessed. The IOP-lowering effect of ONO-9054 in monkeys was analyzed after a single (0.3, 3, or 30 μg/mL) or 7-day repeated (30 μg/mL, every day) topical ocular administration. Ophthalmologic and histopathologic evaluations of the eye were performed after 4-week ocular administration of ONO-9054 (30 μg/mL, twice a day) in monkeys. The ONO-AG-367 exhibited high affinity for both EP3 and FP receptors and potent agonist activity, with EC50 values of 28.6 nM for the EP3 receptor and 22.3 nM for the FP receptor. Single and repeated topical ocular administration of ONO-9054 caused IOP reductions in normotensive monkeys. The maximum IOP reductions on day 7 observed with ONO-9054 (7.3 ± 0.8 mm Hg) were significantly greater than those observed with latanoprost (50 μg/mL, 4.9 ± 0.4 mm Hg) or travoprost (40 μg/mL, 5.1 ± 0.6 mm Hg). In ophthalmologic and histopathologic evaluations, slight ...Continue Reading

Citations

Aug 23, 2016·Expert Opinion on Investigational Drugs·Jed Asher Lusthaus, Ivan Goldberg
Feb 9, 2016·Expert Opinion on Emerging Drugs·Jed Asher Lusthaus, Ivan Goldberg
Jun 21, 2017·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Rajkumar PatilAlok Mitra
Jan 13, 2018·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Najam A Sharif
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Nov 28, 2017·Expert Opinion on Pharmacotherapy·Emily M SchehleinAlan L Robin
Sep 20, 2018·Expert Opinion on Investigational Drugs·Artemis Matsou, Eleftherios Anastasopoulos
Aug 30, 2019·Expert Opinion on Therapeutic Patents·Andrea Angeli, Claudiu T Supuran
Nov 10, 2016·Current Opinion in Ophthalmology·Emily M SchehleinAlan L Robin

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