ACT-462206

Research use only, not for human use.

ACT-462206 is an orally available Orexin 1/Orexin 2 receptor antagonist that crosses the blood-brain barrier.ACT-462206 is highly potent and can be used in studies of sleep and anxiety.

ACT-462206 is an orally active and potent dual Orexin 1/Orexin 2 receptor antagonist with IC50s of 60 nM (Orexin 1) and 11 nM (Orexin 2), respectively. ACT-462206 exhibits brain penetration properties, and can be used for insomnia, stress/anxiety-related disorders and addiction research.

Orexins are released in a Ca2+-sensitive manner at axonal terminals and can then bind to two closely related G-protein-coupled receptors (GPCRs): orexin receptor type 1 (OX1) and orexin receptor type 2 (OX2).ACT-462206 shows binding affinity with Kbs of 17 nM (hOX1), 2.4 nM (hOX2), 28 nM (rOX1), 9.9 nM (rOX2), 27 nM (dOX1), 4.2 nM (dOX2), respectively.ACT-462206 inhibits Orexin activity with IC50s of 60 nM (hOX1), 11 nM (hOX2), 48 nM (rOX1), 9.6 nM (rOX2), 68 nM (dOX1), 26 nM (dOX2), respectively.ACT-462206 inhibits CYP450 3A4T and 3A4M with IC50s of 15 μM and 29 μM, respectively.

ACT-462206 (compound 24) (100 mg/kg; p.o.; sampling at 3 h) can go cross blood brain barrier, with concentrations are 2267 ng/mL and 1219 ng/g in plasma and brain, respectively in male Wistar rats. ACT-462206 (10-300 mg/kg; p.o.; single dose) shows sleep-promoting effects in male Wistar rats and in male Beagle dogs, with decreasing wakefulness and increasing non-rapid eye movement (non-REM) and REM sleep.ACT-462206 (100, 300 mg/kg; p.o.; single dose) exerts anxiolytic-like effects, decreases the fear-potentiated startle reflexes in response to a sudden loud noise in rats, reduces the socialstress-induced increases of locomotion, body temperature, and heart rate.Animal Model:Male Wistar rats Dosage:0, 10, 30, 100, 300 mg/kg Administration: Oral gavage; single dose Result:Decreased the latency to the first persistent episode of non-REM sleep (60 s) and the first persistent episode of REM sleep (30 s).Dose-dependently decreased total wake time and behavioral home cage activity (one-way ANOVA; p <0.001), while increasing REM and non-REM sleep times.

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Others

Other Targets

OX Receptor

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1361321-96-1

388.48

C20H24N2O4S

>98% (HPLC)

In Vitro:?DMSO : ≥ 100 mg/mL (257.41 mM )

COc1ccc(cc1)S(=O)(=O)N1CCC[C@H]1C(=O)Nc1cc(C)cc(C)c1

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(-20℃)

With Ice Pack

≥ 2 years