IPSU

IPSU is a selective, orally available and brain penetrant OX2R antagonist with a pK_i of 7.85. IC50 & Target: pKi: 7.85 (OX2R), 6.29 (OX1R)^[1] In Vitro: Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. IPSU binds rapidly and reaches equilibrium very quickly in binding and/or functional assays^[2]. In Vivo: IPSU has low blood clearance, shows high maximal blood exposure and AUC after oral dosing. It exhibits an acceptable absolute oral bioavailability and a brain/blood concentration ratio that indicated favorable brain penetration. IPSU increases sleep when dosed during the mouse active phase (lights off); IPSU induces sleep primarily by increasing NREM sleep. IPSU shows a fast onset of action, with a clear increase in total sleep time during the first hour afterdosing. The effect lasts 4-5 h, after which time the total sleep time per hour is the same as on vehicle day ^[1].