| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Orexin receptors (OX receptors). Orexin receptor antagonist 2 is a selective antagonist of orexin receptors, exhibiting potent inhibitory activity with pKi values of 7.69 and 9.78 (corresponding to Ki in the low nM range). It inhibits orexin-mediated arousal signaling, reducing wakefulness and promoting sleep.
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| ln Vitro |
Orexin receptor antagonist 2 exhibits potent orexin receptor antagonistic activity with pKi values of 7.69 and 9.78, corresponding to Ki in the low nanomolar range. These values indicate high affinity binding to orexin receptors. The compound is characterized by its potent inhibitory activity and potential for insomnia research.
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| ln Vivo |
No published in vivo efficacy studies are available for orexin receptor antagonist 2. Based on its high-affinity orexin receptor antagonism (pKi = 9.78), it is expected to promote sleep and reduce wakefulness in rodent sleep models such as EEG/EMG-recorded rats or mice. However, such studies have not been reported in the literature. Formal in vivo pharmacodynamic characterization is required.
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| Enzyme Assay |
Cell-free radioligand binding assays for orexin receptors 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 orexin receptor antagonist 2 (0.01 nM to 10 uM) in binding buffer (50 mM HEPES, pH 7.4, 5 mM MgCl2, 0.5% BSA) for 60-90 minutes at 25degC. Bound radioactivity is separated by filtration through GF/B filters, and specific binding is determined with 1 uM unlabeled orexin-A. pKi values of 7.69 and 9.78 are calculated from competition curves.
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| Cell Assay |
HEK293 cells stably expressing human orexin receptors (OX1R or OX2R) are seeded in 384-well plates and loaded with a calcium-sensitive fluorescent dye such as Fluo-4 AM. Cells are pre-incubated with increasing concentrations of the antagonist (0.1-1000 nM) for 10-15 minutes, then stimulated with a submaximal concentration of orexin-A (10-30 nM). Intracellular calcium flux is measured using a FLIPR or FDSS plate reader. IC50 values for antagonism are determined by nonlinear regression. pKi values are calculated using the Cheng-Prusoff equation.
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| Animal Protocol |
No in vivo animal experimental protocols are specifically published for orexin receptor antagonist 2. Standard protocols for orexin antagonists involve oral administration to rats (3-30 mg/kg) prior to lights-on (inactive phase) or lights-off (active phase). Sleep-wake stages are recorded by EEG/EMG telemetry. Parameters include latency to persistent sleep, total sleep time, NREM and REM sleep duration, and wake bout frequency. Such studies would be required to validate the in vivo efficacy.
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| ADME/Pharmacokinetics |
No pharmacokinetic data are reported for orexin receptor antagonist 2. The molecular formula is C25H31N5O2 with molecular weight 433.55 g/mol. Predicted density is 1.28 g/cm3. Recommended storage: powder at -20degC for up to 3 years; in solvent at -80degC for 1 year. The compound can be shipped at ambient temperature with blue ice. Like other small-molecule orexin antagonists, it likely has moderate oral bioavailability and brain penetration, but this has not been confirmed.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for orexin receptor antagonist 2. As a research chemical intended for insomnia research, standard safety assessments would include in vitro hERG channel inhibition to evaluate potential for QT prolongation, CYP inhibition assays for drug-drug interaction potential, and in vivo tolerability studies in rodents. No clinical trials have been conducted.
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| References | |
| Additional Infomation |
Other information: Orexin receptor antagonist 2 (compound 30) is characterized by its potent antagonistic activity with pKi values of 7.69 and 9.78, making it a valuable research tool for insomnia studies. The compound is not an FDA-approved drug and is intended for research use only. It is available from commercial suppliers for investigational purposes. The pKi values indicate sub-nanomolar to low-nanomolar affinity.
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| Molecular Formula |
C25H31N5O2
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|---|---|
| Molecular Weight |
433.54594540596
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| Exact Mass |
433.247
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| CAS # |
1457940-75-8
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| PubChem CID |
72704097
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
657
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2(CCN(C3N=C(C)C=C(C)N=3)CC2)CCCN1CC1=CNC2C=CC(=CC1=2)OC
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| InChi Key |
GKTSTVGKOKZFKP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H31N5O2/c1-17-13-18(2)28-24(27-17)29-11-8-25(9-12-29)7-4-10-30(23(25)31)16-19-15-26-22-6-5-20(32-3)14-21(19)22/h5-6,13-15,26H,4,7-12,16H2,1-3H3
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| Chemical Name |
9-(4,6-dimethylpyrimidin-2-yl)-2-[(5-methoxy-1H-indol-3-yl)methyl]-2,9-diazaspiro[5.5]undecan-1-one
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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: 62.5 mg/mL (144.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.80 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 20.8 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: ≥ 2.08 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3065 mL | 11.5327 mL | 23.0654 mL | |
| 5 mM | 0.4613 mL | 2.3065 mL | 4.6131 mL | |
| 10 mM | 0.2307 mL | 1.1533 mL | 2.3065 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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