Orexin OX2 receptor agonists have demonstrated the ability to enhance wakefulness in rodent models, as well as in nonhuman primates and patients with narcolepsy and idiopathic hypersomnia. Based on recent findings, it has been hypothesized that they may also regulate cognition, mood and other neuropsychiatric functions. Furthermore, dysregulated orexin signaling has been reported in patients with major depressive disorder (MDD) with suicide attempts.
Takeda Pharmaceutical Co. Ltd. has synthesized heterocyclic compounds acting as orexin OX2 receptor (OX2R; HCRTR2) agonists reported to be useful for the treatment of narcolepsy, among others.
Idorsia Pharmaceuticals Ltd. has identified aryl sulfone and sulfanone derivatives acting as orexin OX2 receptor (HCRTR2) agonists reported to be useful for the treatment of eating disorders, fatigue, Kleine-Levin syndrome, narcolepsy, obesity, pain, and psychiatric and inflammatory disorders, among others.
At the 2025 World Sleep Congress, researchers from Bioprojet SA, Harmony Biosciences Holdings Inc. and Teijin Pharma Ltd. presented preclinical efficacy data on BP1.15205, a novel, orally available OX2R agonist under development for the treatment of narcolepsy.
Idorsia Pharmaceuticals Ltd. has patented macrocyclic compounds acting as orexin OX2 receptor agonists reported to be useful for the treatment of obesity, pain, fatigue, inflammation, cognitive, sleep, eating and mood disorders.
Idorsia Pharmaceuticals Ltd. has synthesized aryl sulfone and sulfanone derivatives acting as orexin OX2 receptor agonists reported to be useful for the treatment of eating disorders, fatigue, Kleine-Levin syndrome, narcolepsy, obesity, pain, and psychiatric and inflammatory disorders, among others.
Teijin Pharma Ltd. has identified crystalline forms of oxazepine derivatives acting as orexin OX2 receptor agonists reported to be useful for the treatment of narcolepsy, hypersomnia and sleep apnea.
Spiromacrocyclic compounds acting as orexin OX2 receptor agonists have been described in an H. Lundbeck A/S patent and reported to be useful for the treatment of type 1 and type 2 narcolepsy.
Centessa Pharmaceuticals plc recently detailed the discovery and preclinical characterization of a novel potent and selective orexin OX2 receptor agonist, ORX-142.
