L826266

L826266 is a potent and selective small molecule antagonist of the Prostaglandin E receptor 3 (EP3). Developed by Merck Frosst, it belongs to the biaryl acylsulfonamide class of compounds. The drug was primarily utilized in preclinical research to elucidate the role of the EP3 receptor in mediating sensory nerve activation and the cough reflex induced by prostaglandin E2 (PGE2). In experimental models, L826266 has been shown to concentration-dependently inhibit PGE2-induced depolarization in isolated vagus nerves from humans, mice, and guinea pigs. Furthermore, in vivo studies in conscious guinea pigs demonstrated that systemic administration of L826266 significantly attenuates PGE2-induced cough. Its development serves as a proof-of-concept for creating PGE2 analogs or related therapies that provide anti-inflammatory and bronchodilatory benefits for airway diseases like asthma and COPD without the dose-limiting side effect of cough.