ACT 335827

ACT-335827 is a selective, orally active, brain-penetrant orexin type 1 receptor antagonist. ACT-33582 acts on OXR1 and OXR2 with IC50 values of 6 nM and 417 nM, respectively. ACT-33582 can be used in studies related to neurological disorders[1].

Signaling Pathways >> GPCR/G Protein >> Orexin Receptor (OX Receptor)

Research Areas >> Neurological Disease

OX1:6 nM (IC50)

OX2:417 nM (IC50)

ACT-335827 (0-10 μM, 2 h) acts on OXR-1 and OXR-2 with the Kb values of 41 nM and 560 nM, the IC50 values of 120 nM and 2300 nM, respectively in CHO cells[1].

ACT-335827 (oral gavage, 30-100 mg/kg, once) can reduce the fear-induced startle response with no affecting motor or cognitive function in rats[1]. ACT-335827 (oral administration, 300 mg/kg, everyday, 4 weeks) has less effect on metabolic syndrome (MetS), such as diet-induced obesity (DIO) in male Wistar rats[2]. Animal Model: Rats[1] Dosage: 30, 100 or 300 mg/kg Administration: Oral gavage; once Result: Reduced fear-induced startle response at 300 mg/kg. Decreased stress-induced elevated body temperature at 300 mg/kg and accelerated heat rate at 100 or 300 mg/kg but no effect on locomotion and blood pressure. Animal Model: Male Wistar rats weighing160-180g[2] Dosage: 300 mg/kg Administration: Oral administration; everyday; 4 weeks Result: Reduced preference for high fat/sweet diets but no effect on absolute energy intake. Increased water intake and HDL relative to total cholesterol. Resulted in a 4% weight gain compared to the control group.

[1]. Michel A Steiner, et al. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist. ChemMedChem. 2013 Jun;8(6):898-903.

[2]. Michel A Steiner, et al. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome. Front Pharmacol. 2013 Dec 30;4:165.