Therapeutics: Orexin 2 receptor (OX2R; HCRTR2)

Cell culture and mouse studies identified an OX2R activator that could help treat cataplexy and narcolepsy. Screening of a small molecule library in a mammalian cell-based assay of OX2R-mediated calcium signaling and optimization of hits identified a sulfonamide compound that activated OX2R-mediated calcium signaling with an EC50 of 23 nM. In normal mice, a water-soluble analog of the compound increased cumulative wake time during the inactive phase of the mouse sleep cycle compared with vehicle. Next steps include optimizing the sulfonamide compound...