ACT-462206 是一种口服有效的双 Orexin 1/Orexin 2 受体拮抗剂，IC₅₀ 分别为 60 nM (Orexin 1) 和 11 nM (Orexin 2)。ACT-462206 能穿过血脑屏障，可用于失眠、压力/焦虑相关障碍和成瘾研究。

ACT-462206 is an orally active and potent dual Orexin 1/Orexin 2 receptor antagonist with IC 50 s 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.

Solid

OX2 OX1

Orexins are released in a Ca-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. has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Pharmacokinetics in different species

Room temperature in continental US; may vary elsewhere.

4°C, protect from light In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

[1]. Boss C, et al. Structure-activity relationship, biological, and pharmacological characterization of the proline sulfonamide ACT-462206: a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. ChemMedChem. 2014 Nov;9(11):2486-96.

In Vitro: DMSO : ≥ 100 mg/mL (257.41 mM)配制储备液