OX1 Receptor
OX1 receptor (OX1R/HCRTR1) is a G protein-coupled orexin receptor activated by hypothalamic orexin-A and orexin-B, linking orexin signaling to feeding behavior, wakefulness, reward processing, emotion, and energy homeostasis[1][2]. Mechanistically, OX1R belongs to the orexin receptor system that activates intracellular Ca2+-linked signaling and supports arousal-related neural circuits[1][2]. In disease models, OX1R signaling is relevant to panic anxiety because systemic OX1 receptor antagonists blocked panic responses in a rat model, and human subjects with panic anxiety showed elevated cerebrospinal-fluid orexin[3]. OX1R also supports addiction-related behavior, because OX1R antagonism reduced heroin self-administration and cue-induced heroin seeking in rats[4]. Compared with OX2R, OX1R shows a distinct ligand profile, with higher affinity for orexin-A than orexin-B, while OX2R binds both orexin peptides with similar affinities[1][5]. For experimental applications, SB-334867-A is a non-peptide OX1-selective receptor antagonist, and JNJ-61393215 is a selective OX1R antagonist evaluated in rat and human panic models[6][7].
References:
- [1]. Sakurai T, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998 Feb 20;92(4):573-85. [Content Brief]
- [2]. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007 Mar;8(3):171-81. doi: 10.1038/nrn2092. Epub 2007 Feb 14. PMID: 17299454. et al. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007 Mar;8(3):171-81. [Content Brief]
- [3]. Johnson PL, et al. A key role for orexin in panic anxiety. Nat Med. 2010 Jan;16(1):111-5. [Content Brief]
- [4]. Smith RJ, et al. Orexin / hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking. Eur J Neurosci. 2012 Mar;35(5):798-804. [Content Brief]
- [5]. Mieda M, et al. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci. 2011 Apr 27;31(17):6518-26. [Content Brief]
- [6]. Smart D, et al. SB-334867-A: the first selective orexin-1 receptor antagonist. Br J Pharmacol. 2001 Mar;132(6):1179-82. [Content Brief]
- [7]. Salvadore G, et al. Translational evaluation of novel selective orexin-1 receptor antagonist JNJ-61393215 in an experimental model for panic in rodents and humans. Transl Psychiatry. 2020 Sep 7;10(1):308. [Content Brief]
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OX1 Receptor Related Products (33)
Related Products (33)
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Orexin A (human, rat, mouse)
0 ImagesSynonyms: Hypocretin-1 (human, rat, mouse)Orexin A (human, rat, mouse) (Hypocretin-1 (human, rat, mouse)), a 33 amino acid excitatory neuropeptide, orchestrates diverse central and peripheral processes. Orexin A (human, rat, mouse) binds and activates two types of G protein-coupled receptors, the orexin-1 receptor (OX1R) and the orexin-2 receptor (OX2R). Orexin A (human, rat, mouse) has a role in the regulation of feeding behavior. Orexin A (human, rat, mouse) is an effective anti-nociceptive and anti-hyperalgesic agent in mice and rats.
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SB-334867
0 ImagesSynonyms: SB 334867ASB-334867 (SB 334867A) is an excellent,selective and blood-brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pKb=7.4), 100-fold over 5-HT2B, 5-HT2C with pKi 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.
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Almorexant
0 ImagesSynonyms: ACT 078573Almorexant (ACT 078573) is an orally active, potent and competitive dual orexin receptor antagonist, with Kd 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.
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Orexin A (human, rat, mouse) acetate
0 ImagesCat. No.: HY-106224BPurity: 99.53%Synonyms: Hypocretin-1 (human, rat, mouse) acetateOrexin A (Hypocretin-1) (human, rat, mouse) acetate is a hypothalamic neuropeptide with analgesic properties (crosses the blood-brain barrier). Orexin A (human, rat, mouse) acetate binds and activates two types of G protein-coupled receptors, the orexin-1 receptor (OX1R) and the orexin-2 receptor (OX2R). Orexin A (human, rat, mouse) acetate can be used in studies of appetite regulation, neurodegenerative diseases and modulation of injurious messaging.
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Oveporexton
0 ImagesSynonyms: TAK-861Oveporexton (TAK-861) is an orally active and selective orexin receptor 2 (OX2R) agonist with an EC50 of 2.5 nM. Oveporexton exhibits 3000-fold selectivity for OX2R over OX1R. Oveporexton can be used for the study of hypersomnia disorders including narcolepsy.
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Almorexant hydrochloride
0 ImagesSynonyms: ACT 078573 hydrochlorideAlmorexant (ACT 078573) hydrochloride is an orally active, potent and competitive dual orexin receptor antagonist, with Kd 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.
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Orexin A (human, rat, mouse) TFA
0 ImagesCat. No.: HY-106224APurity: 98.13%Synonyms: Hypocretin-1 (human, rat, mouse) TFAOrexin A (human, rat, mouse) (Hypocretin-1 (human, rat, mouse)) TFA, a 33 amino acid excitatory neuropeptide, orchestrates diverse central and peripheral processes. Orexin A (human, rat, mouse) TFA binds and activates two types of G protein-coupled receptors, the orexin-1 receptor (OX1R) and the orexin-2 receptor (OX2R). Orexin A (human, rat, mouse) TFA has a role in the regulation of feeding behavior. Orexin A (human, rat, mouse) TFA is an effective anti-nociceptive and anti-hyperalgesic agent in mice and rats.
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RTIOXA-43
0 ImagesRTIOXA-43 is a orexin receptor agonist with EC50s of 24 nM and 24 nM for OX2 and OX1 receptors, respectively.
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MK-1064
0 ImagesMK-1064 is a selective and orally active OX2R antagonist (Ki: 0.5 nM, IC50: 18 nM). MK-1064 promotes sleep in vivo. MK-1064 can be used in the research of insomnia.
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SB-674042
0 ImagesSB-674042 is a potent and selective non-peptide orexin OX1 receptor antagonist (Kd=5.03 nM), exhibits 100-fold selectivity for OX1 over OX2 receptors with IC50 values of 3.76 nM and 531 nM, respectively.
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SB-408124
0 ImagesSB-408124 is a non-peptide OX1 receptor antagonist with Kis of 57 nM and 27 nM in whole cell and membrane, respectively. SB-408124 exhibits 50-fold selectivity over OX2 receptor.
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OXA(17-33)
0 ImagesCat. No.: HY-P1341CAS No.: 343268-91-7Synonyms: Orexin A (17-33) (human, mouse, rat, bovine)OXA (17-33) (Orexin A (17-33) (human, mouse, rat, bovine)) is the shortest active orexin peptide that selectively targets OX1 (EC50=8.29 nM), with 23-fold selectivity for the OX1 receptor over the OX2 receptor. The activity of OXA (17-33) depends on the Tyr17, Leu20, Asn25, His26 residues and the spatial conformation of the α-helix. OXA (17-33) activates signaling pathways involving inositol-1,4,5-trisphosphate receptor (IP3R), phospholipase D (PL-D) and choline-Sigma-1R, thereby increasing the cytoplasmic Ca2+ level in nucleus accumbens neurons, an effect that is blocked by Sigma-1R antagonists. OXA (17-33) serves as an important biological probe for investigating the function of the OX1 receptor. OXA (17-33) can be modified via incorporation of mixed disulfide bonds of homocysteine and cysteamine, and is widely used in studies related to insomnia and narcolepsy.
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TCS 1102
0 ImagesTCS 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.
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(R)-YNT-3708
0 Images(R)-YNT-3708 is a selective orexin 1 (OX1R) agonist, with an EC50 of 7.48 nM. (R)-YNT-3708 has antinociceptive effects.
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SB-334867 free base
0 ImagesSynonyms: SB334867A free baseSB-334867 free base (SB334867A free base) is an excellent, selective and blood–brain barrier permeable orexin-1 (OX1) receptor antagonist, shows selectivity over OX2 (pKb=7.4), 100-fold over 5-HT2B, 5-HT2C with pKi 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.
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GSK1059865
0 ImagesGSK1059865 is a potent orexin 1 receptor antagonist.
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Fazamorexant
0 ImagesSynonyms: YZJ-1139Fazamorexant (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.
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JNJ-54717793
0 ImagesJNJ-54717793, as a brain penetrant, is an orally active, selective and high affinity orexin-1 receptor (OX1R) antagonist (plasma EC50=85 ng/mL). The Ki 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.
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ACT-462206
0 ImagesACT-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.
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