Orexin Receptor (OX Receptor) Antagonist

SB-334867 (SB 334867A) is an excellent,selective and blood-brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pK_b=7.4), 100-fold over 5-HT_2B, 5-HT_2C with pK_i values of 5.4 and 5.3, respectively. SB-334867 reduces ethanol consumption and inhibits the acquisition of morphine-induced sensitization to locomotor activity in vivo.

Almorexant (ACT 078573) is an orally active, potent and competitive dual orexin receptor antagonist, with K_d values of 1.3 nM (OX1) and 0.17 nM (OX2), respectively. Almorexant reversibly blocks signaling of orexin-A and orexin-B peptides. Almorexant totally blocked the intracellular Ca²⁺ signal pathway. Almorexant stimulates caspase-3 activity in AsPC-1 cells and induces apoptosis.

Balumorexton is an orally active orexin type 2 receptor (OX2R) agonist. Balumorexton is used for the research of narcolepsy.

Seltorexant (JNJ-42847922) is an orally active, high-affinity, and selective orexin-2 receptor (OX2R) antagonist (pK_i values of 8.0 and 8.1 for human and rat OX2R). Seltorexant (JNJ-42847922) crosses the blood-brain barrier and quickly occupies OX2R binding sites in the rat brain.

Vornorexant (ORN-0829; TS-142) is a potent dual OX1R and OX2R antagonist with IC50 values of 1.05 nM and 1.27 nM, respectively. Vornorexant exhibits potent sleep-promoting effects in vivo and can be used for insomnia research research.

TCS-OX2-29 is a potent, high affinities and selective orexin-2 receptor (OX₂R) antagonist with an IC₅₀ value of 40 nM and a pK_I value of 7.5. TCS-OX2-29 displays ~250-fold selectivity for OX₂ over OX₁.

Filorexant (MK-6096) is an orally bioavailable potent and selective reversible antagonist of OX1 and OX2 receptor(<3 nM in binding).

Almorexant (ACT 078573) hydrochloride is an orally active, potent and competitive dual orexin receptor antagonist, with K_d values of 1.3 nM (OX1) and 0.17 nM (OX2), respectively. Almorexant hydrochloride reversibly blocks signaling of orexin-A and orexin-B peptides. Almorexant hydrochloride totally blocked the intracellular Ca²⁺ signal pathway. Almorexant hydrochloride stimulates caspase-3 activity in AsPC-1 cells and induces apoptosis.

MK-1064 is a selective and orally active OX₂R antagonist (K_i: 0.5 nM, IC₅₀: 18 nM). MK-1064 promotes sleep in vivo. MK-1064 can be used in the research of insomnia.

JNJ-10397049 is a potent and selective orexin 2 receptor (OX₂R) antagonist, with a pK_i of 8.3. JNJ-10397049 is 600-fold selective for the OX₂R over the OX₁R.

SB-674042 is a potent and selective non-peptide orexin OX₁ receptor antagonist (K_d=5.03 nM), exhibits 100-fold selectivity for OX₁ over OX₂ receptors with IC₅₀ values of 3.76 nM and 531 nM, respectively.

EMPA is a high-affinity, reversible and selective orexin OX₂ receptor antagonist. [³H]EMPA binds to human and rat OX₂-HEK293 membranes with K_D values of 1.1 and 1.4 nM respectively.

SB-408124 is a non-peptide OX1 receptor antagonist with K_is of 57 nM and 27 nM in whole cell and membrane, respectively. SB-408124 exhibits 50-fold selectivity over OX2 receptor.

Seltorexant hydrochloride (JNJ-42847922 hydrochloride) is an orally active, high-affinity, and selective OX2R antagonist (pK_i values of 8.0 and 8.1 for human and rat OX2R). Seltorexant hydrochloride crosses the blood-brain barrier and quickly occupies OX2R binding sites in the rat brain.

TCS 1102 is a potent, dual orexin receptor antagonist, with Ki values of 0.2 nM and 3 nM for OX2 and OX1 receptors, respectively. TCS 1102 demonstrates excellent blood-brain barrier penetrability and moderate bioavailability in rats.

SB-334867 free base (SB334867A free base) is an excellent, selective and blood–brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pK_b=7.4), 100-fold over 5-HT_2B, 5-HT_2C with pK_i values of 5.4 and 5.3, respectively. SB-334867 reduces ethanol consumption and inhibits the acquisition of morphine-induced sensitization to locomotor activity in vivo.

GSK1059865 is a potent orexin 1 receptor antagonist.

Fazamorexant (YZJ-1139) is an orally active dual orexin receptor antagonist, with an IC₅₀ of 32 nM against OX1R and an IC₅₀ of 41 nM against OX2R. Fazamorexant prolongs total sleep time and improves sleep efficiency. Fazamorexant is applicable to related research on insomnia.

JNJ-54717793, as a brain penetrant, is an orally active, selective and high affinity orexin-1 receptor (OX1R) antagonist (plasma EC₅₀=85 ng/mL). The K_i values of JNJ-54717793 for hOX1R (human OX1R) and hOX2R are 16 nM and 700 nM, respectively. JNJ-54717793 is a potent compound of anxiety disorders.

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.