ACT-335827 is an orally available, brain-penetrant, orexin type 1 receptor-selective antagonist, with IC50 values of 6 nM for OXR1 and 417 nM for OXR2. It is suitable for studies related to neurological disorders [1].

OX2:417 nM, OX1:6 nM

ACT-335827 (0-10 μM, 2 h) demonstrates activity on OXR-1 (Kb = 41 nM, IC50 = 120 nM) and OXR-2 (Kb = 560 nM, IC50 = 2300 nM) in CHO cells [1].

ACT-335827 administered through oral gavage at doses ranging from 30-100 mg/kg once, effectively reduces the fear-induced startle response in rats, without impacting their motor or cognitive functions [1]. In contrast, continuous oral administration of ACT-335827 at a dose of 300 mg/kg daily for four weeks shows diminished effects on metabolic syndrome (MetS) symptoms, such as diet-induced obesity (DIO), in male Wistar rats [2]. Notably, the compound at 300 mg/kg reduces the preferential selection for high fat/sweet diets, increases water intake, and elevates HDL levels relative to total cholesterol, all while only resulting in a modest 4% weight gain compared with control subjects. Furthermore, it's reported that a 300 mg/kg dosage can diminish stress-induced elevations in body temperature and accelerate heart rate at both the 100 and 300 mg/kg doses, with no observable effects on locomotion and blood pressure.