| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
OX2 Receptor
OX1R and OX2R (dual orexin receptor antagonist). Vornorexant antagonizes both orexin receptor subtypes, inhibiting the wake-promoting effects of endogenous orexin neuropeptides to facilitate sleep initiation and maintenance. |
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| ln Vitro |
Vornorexant is a potent dual OX1R and OX2R antagonist with IC50 values of 1.05 nM for OX1R and 1.27 nM for OX2R. It shows potent sleep-promoting effects in animal models and can be utilized to study insomnia mechanisms and the role of orexin signaling in sleep-wake regulation.
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| ln Vivo |
At a po, vornorexant (oral dosage; 1–10 mg/kg) shows strong sleep-promoting properties. in a rat polysomnogram study at a dosage of 1 mg/kg. The proportion of total sleep increases in a dose-dependent manner as a result[1]. In rats and dogs, vornorexant has ideal PK characteristics, including a quick Tmax and brief half-lives. In rats and dogs, the T1/2 is 0.238 hours and 1.16 hours, respectively[1].
Vornorexant exhibits potent sleep-promoting effects in animal models. In a rat polysomnogram study at an oral dose of 1 mg/kg, vornorexant increases total sleep time in a dose-dependent manner (1-10 mg/kg). The proportion of total sleep increases as the dosage increases. In rats and dogs, vornorexant has ideal PK characteristics including rapid Tmax and short half-lives. |
| Enzyme Assay |
Cell-free radioligand binding assays for OX1R and OX2R are performed using membranes from CHO-K1 cells stably expressing human orexin receptors. Membrane preparations (10-20 ug) are incubated with 0.1 nM [125I]-orexin-A and increasing concentrations of vornorexant (0.01 nM to 10 uM) in binding buffer (50 mM HEPES, pH 7.4, 5 mM MgCl2, 0.5% BSA) for 60-90 min at 25degC. Bound radioactivity is separated by filtration through GF/B filters, and specific binding is defined with 1 uM unlabeled orexin-A. IC50 values are calculated by nonlinear regression and converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
HEK293 cells stably expressing human OX1R or OX2R are seeded and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with vornorexant at increasing concentrations (0.01-1000 nM) for 10-15 minutes, then stimulated with a submaximal concentration of orexin-A (10-30 nM). Intracellular calcium flux is measured in real-time using a FLIPR. IC50 values for antagonism are calculated as the concentration required to inhibit 50% of the orexin-A-induced calcium response.
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| Animal Protocol |
Animal/Disease Models: Rat[1]
Doses: 1, 3, 10 mg/kg Route of Administration: Oral administration to rats prior to turning the light off (start of the active phase); 1-10 mg/kg Experimental Results: Possessed promising sleep-inducing and sleep-promoting effects. In vivo pharmacodynamics are assessed in male Sprague-Dawley rats using polysomnography (EEG/EMG recording). Vornorexant is administered orally at doses of 1, 3, and 10 mg/kg prior to lights off (the start of the active phase). Sleep parameters including latency to persistent sleep, total sleep time, NREM sleep duration, and REM sleep duration are recorded for 6-8 hours post-dose. For PK studies, vornorexant is administered to rats (IV 1 mg/kg; PO 3-10 mg/kg) and dogs. Blood samples are collected at predetermined time points (0-24 h) for LC-MS/MS analysis. |
| ADME/Pharmacokinetics |
PK properties: In rats, T1/2 = 0.238 hours; in dogs, T1/2 = 1.16 hours. Vornorexant has ideal PK characteristics including rapid absorption (Tmax = 0.25-0.5 h in rats) and short half-life for a rapid-onset/rapid-offset profile. Oral bioavailability is moderate. Volume of distribution and clearance are consistent with a compound designed for sleep induction without next-day residual effects. Metabolism is primarily via CYP3A4.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for vornorexant. As a dual orexin receptor antagonist belonging to the same class as suvorexant and lemborexant, which are FDA-approved for insomnia, the class effect includes potential for next-day somnolence, sleep paralysis, and cataplexy-like symptoms. Standard safety assessments would include hERG channel inhibition, CYP inhibition, and CNS safety pharmacology. Long-term studies would evaluate abuse potential and dependence liability.
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| References | |
| Additional Infomation |
Vornorexant is a small molecule drug. The INN stem "-orexant" in its name indicates that Vornorexant is an orexin receptor antagonist. The monoisotopic molecular weight of Vornorexant is 447.18 Da.
Other information: Vornorexant is a research compound and has not received FDA approval. It belongs to the DORA class of insomnia drugs, which includes suvorexant (Belsomra) and lemborexant (Dayvigo). The compound is available for research purposes only and is not for human consumption. It is useful for studying the role of orexin signaling in sleep-wake regulation and for developing new insomnia therapeutics with rapid-on/rapid-off profiles. |
| Molecular Formula |
C23H22FN7O2
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|---|---|
| Molecular Weight |
447.464887142181
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| Exact Mass |
447.181
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| CAS # |
1517965-94-4
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| PubChem CID |
137419776
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| Appearance |
White to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
667
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=CN=C(C=C1)C1C=CN(C[C@H]2N(C(C3=CC(C)=CC=C3N3N=CC=N3)=O)CCCO2)N=1
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| InChi Key |
AEZZJXJIJFSUEM-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C23H22FN7O2/c1-16-3-6-21(31-26-8-9-27-31)18(13-16)23(32)30-10-2-12-33-22(30)15-29-11-7-20(28-29)19-5-4-17(24)14-25-19/h3-9,11,13-14,22H,2,10,12,15H2,1H3/t22-/m0/s1
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| Chemical Name |
[(2S)-2-[[3-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (223.48 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2348 mL | 11.1742 mL | 22.3484 mL | |
| 5 mM | 0.4470 mL | 2.2348 mL | 4.4697 mL | |
| 10 mM | 0.2235 mL | 1.1174 mL | 2.2348 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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