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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YNT-185 dihydrochloride
0 ImagesYNT-185 dihydrochloride is a nonpeptide, selective orexin type-2 receptor (OX2R) agonist, with EC50s of 0.028 and 2.75 μM for OX2R and OX1R, respectively. YNT-185 dihydrochloride ameliorates narcolepsy-cataplexy symptoms in mouse models.
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Nivasorexant
0 ImagesSynonyms: ACT-539313Nivasorexant (ACT-539313) is an orally active, blood-brain barrier penetrant, selective orexin OX1R inhibitor. Nivasorexant specifically blocks central OX1Rs without affecting OX2Rs, and exhibits competitive inhibitory activity against CYP2C8, CYP2C9, CYP2C19 and CYP3A4 (IC50 values are 25 μM, 8.6 μM, 1.6 μM, 19 μM/44 μM, respectively). Nivasorexant significantly reduces binge-like eating behavior of highly palatable food in rat models and has long-acting properties. Nivasorexant shows no relevant off-target activity against over 130 selected proteins, exhibits favorable safety profiles, and can be used for studies related to binge eating disorder.
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[Ala11,D-Leu15]-Orexin B(human)
![[Ala11,D-Leu15]-Orexin B(human)](https://file.medchemexpress.com/product_pic/hy-p1340.gif "Click to View [Ala11,D-Leu15]-Orexin B(human) Product Detail")
0 Images[Ala11,D-Leu15]-Orexin B(human) is a potent and selective orexin-2 receptor (OX2) agonist. [Ala11,D-Leu15]-Orexin B(human) shows a 400-fold selectivity for the OX2 (EC50=0.13 nM) over OX1 (52 nM).
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SB-408124 Hydrochloride
0 ImagesSB-408124 Hydrochloride is a selective non-peptide orexin receptor 1 (OX1) receptor antagonist with Kis of 57 nM and 27 nM in whole cell and membrane, respectively. SB-408124 Hydrochloride exhibits 50-fold selectivity over OX2 receptor.
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ACT-335827
0 ImagesACT-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.
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OX-201
0 ImagesCat. No.: HY-162712CAS No.: 2460722-03-4OX-201 is an orally active, blood-brain barrier-permeable OX2R agonist with an EC50 of 8.0 nM. OX-201 activates OX2R to induce wakefulness and neuronal activation. OX-201 promotes the release of neuron activity-dependent tau protein from neurons into the interstitial fluid of hippocampal tissues. OX-201 is applicable to research related to Alzheimer's disease and tauopathies.
![[Ala11,D-Leu15]-Orexin B(human) TFA](https://file.medchemexpress.com/product_pic/hy-p1340a.gif "Click to View [Ala11,D-Leu15]-Orexin B(human) TFA Product Detail")
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Ledasorexton
0 ImagesCat. No.: HY-177096CAS No.: 2758363-88-9Ledasorexton is an orally active OX2R agonist (EC50: 0.99 nM). Ledasorexton has awakening effect in mice. Ledasorexton can be used for research of neurological disease.
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Hypocretin (70-98), human
0 ImagesCat. No.: HY-P3867CAS No.: 1129545-33-0Hypocretin (70-98), human is a polypeptide that is capable of binding to an orexin receptor OX1R and promotes apoptosis.
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Orexin receptor antagonist 4
0 ImagesCat. No.: HY-146517CAS No.: 2251017-69-1Orexin receptor antagonist 4 is potent and selective orexin 2 receptor (OX2R) antagonist with an IC50 of 4.27 nM. Orexin receptor antagonist 4 is 61-fold selective for the OX2R over the OX1R (IC50 of 295 nM) (WO2018206959A1; example 1).
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Orexin receptor antagonist 7
0 ImagesCat. No.: HY-177790CAS No.: 2096315-41-0Orexin receptor antagonist 7 (Compound 34) is an antagonist of the orexin receptor (OX1R), with a Ki value of 4.05 nM. Orexin receptor antagonist 7 shows no detectable activity towards OX2R and has very low affinities for the three opioid receptors (μ, δ, κ) (Ki > 1,000 nM). Orexin receptor antagonist 7 can be used for research on opioid addiction.
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Orexin 1 receptor modulator-1
0 ImagesCat. No.: HY-184879CAS No.: 1628320-31-9Orexin 1 receptor modulator-1 is a highly potent and selective modulator of the orexin 1 receptor (OX1R), with a Ki value of 4 nM for both rat OX1R and human OX1R, and a Ki value of 767 nM for human OX2R. Orexin 1 receptor modulator-1 can be used in studies related to the orexin signaling pathway and the nervous system.
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