OX₂ Receptor Antagonist

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.

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.

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

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.

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.

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.

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.

CVN766 is an orally active inhibitor of orexin 1 receptor antagonist with blood-brain permeability with the IC₅₀ values of 8 nM and >10 μM for OX1R and OX2R, respectively. CVN766 can be used for study schizophrenia.

Valerosidate is an OX2R antagonist. Valerosidate increases expression of tumor suppressor proteins p53 and PTEN, selectively reduces colon cancer cell viability, and suppresses colon cancer cell migration. Valerosidate can be used for the research of colon cancer and insomnia.

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.

MK-3697 is an orally active orexin 2 receptor (OX2R) antagonist, with an IC₅₀ value of 16 nM and a K_i value of 1.1 nM against human OX2R. MK-3697 blocks the wake-promoting OX2R signaling pathway, reduces active wake time, and increases slow-wave sleep and rapid eye movement sleep time in mice, rats and dogs. MK-3697 can be used for research on insomnia.