OX2 Receptor
OX2 receptor (OX2R/HCRTR2) is a class A G protein-coupled receptor activated by orexin-A and orexin-B, two hypothalamic neuropeptides derived from prepro-orexin[1]. Mechanistically, this orexin receptor system links hypothalamic neuropeptide signaling to feeding behavior, arousal biology, and sleep-wake regulation[1][2]. In disease models, loss of orexin signaling produces narcolepsy-like phenotypes, and orexin knockout mice show disrupted sleep regulation[2]. Receptor-specific models further show that OX2R deficiency and orexin- states produce distinct narcolepsy syndromes, supporting OX2R as a central node for non-REM and REM sleep regulatory processes[3]. Compared with OX1R, OX2R remains especially important because orexin-B displays stronger functional preference for OX2R, while both receptor subtypes mediate overlapping but separable orexin biology[1][3]. Structural studies of human OX2R bound to suvorexant define an orthosteric antagonist-binding pocket that supports rational ligand design for sleep and wake research[4]. For experimental applications, the nonpeptide OX2R-selective agonist YNT-185 ameliorated narcolepsy-cataplexy symptoms in mouse models, providing pharmacological proof of concept for OX2R activation[5]. Clinically, an oral OX2R-selective agonist improved sleepiness and cataplexy measures in narcolepsy type 1 but was associated with liver safety limitations[6].
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]. Chemelli RM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999 Aug 20;98(4):437-51. [Content Brief]
- [3]. Willie JT, et al. Distinct narcolepsy syndromes in Orexin receptor-2 and Orexin null mice: molecular genetic dissection of Non-REM and REM sleep regulatory processes. Neuron. 2003 Jun 5;38(5):715-30. [Content Brief]
- [4]. Yin J, et al. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature. 2015 Mar 12;519(7542):247-50. [Content Brief]
- [5]. Irukayama-Tomobe Y, et al. Nonpeptide orexin type-2 receptor agonist ameliorates narcolepsy-cataplexy symptoms in mouse models. Proc Natl Acad Sci U S A. 2017 May 30;114(22):5731-5736. [Content Brief]
- [6]. Dauvilliers Y, et al. Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1. N Engl J Med. 2023 Jul 27;389(4):309-321. [Content Brief]
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OX2 Receptor Related Products (56)
Related Products (56)
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TCS-OX2-29 hydrochloride
0 ImagesCat. No.: HY-100452ACAS No.: 1610882-30-8Synonyms: OX2R antagonistTCS-OX2-29 (hydrochloride) is a potent, high affinities and selective orexin-2 receptor (OX2R) antagonist with an IC50 value of 40 nM and a pKI value of 7.5. TCS-OX2-29 displays ~250-fold selectivity for OX2 over OX1.
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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.
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OX2-2303
0 ImagesCat. No.: HY-178871CAS No.: 1607428-33-0OX2-2303 is a potent, selective orexin-2 receptor (OX2R) antagonist. OX2-2303 exhibits excellent binding affinity towards OX2R (Ki = 0.1 nM), and shows >890-fold selectivity over OX1R. OX2-2303 can be used as a positron emission tomography (PET) radioligand for central nervous system (CNS) research.
![[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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Orexin 2 Receptor Agonist 3
0 ImagesCat. No.: HY-172672Orexin 2 Receptor Agonist 3 (Compound 57) is an orally active and brain-penetrant orexin receptor type-2 (OX2) agonist (EC50: 2.5 nM). Orexin 2 Receptor Agonist 3 increases wakefulness in the orexin/ataxin-3 NT1 mouse model and healthy beagle dogs. Orexin 2 Receptor Agonist 3 can be used in the study of narcolepsy.
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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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OX2R-IN-3
0 ImagesCat. No.: HY-161567CAS No.: 2791360-37-5OX2R-IN-3 (Compound 53) is an orally active type 2 orexin receptor (OX2R) agonist (EC50<100 nM.).
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Fumiporexant
0 ImagesCat. No.: HY-177085CAS No.: 2839408-03-4Fumiporexant (Compound Example 93) is an orally active, brain-penetrant and selective Orexin receptor 2 (OX2R) antagonist. Fumiporexant regulates the sleep-wake cycle and emotion-related pathways in the central nervous system. Fumiporexant is promising for research of nervous system diseases such as insomnia and major depressive disorder.
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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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OX2R-IN-1
0 ImagesCat. No.: HY-149014CAS No.: 2639148-08-4OX2R-IN-1 (compound 15) is a low cytotoxicity profile OX2R-IN-1 antagonist (a potential OX2R binder) with an IC50 value of 484 μM. OX2R-IN-1 (compound 15) can cross the BBB into the brain with a short half-life.
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OX2R agonist 3
0 ImagesCat. No.: HY-163276OX2R agonist 3 (compound 63c) is an agonist for orexin receptor type 2 (OX2R) with EC50 of 339 nM. OX2R agonist 3 is able to cross the blood-brain barrier and exhibits no cytotoxicity in cells
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OX2R agonist-4
0 ImagesCat. No.: HY-187354CAS No.: 3132407-42-9OX2R agonist-4 is an orexin receptor type 2 (OX2R) agonist with an EC50 value of 0.061 nM against human OX2R. OX2R agonist-4 can be used in studies related to narcolepsy.
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MK-8133
0 ImagesCat. No.: HY-123737CAS No.: 1431472-56-8MK-8133 is an orexin-2 receptor antagonist. MK-8133 can be used in the study of insomnia.
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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.
