| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
The primary target of NS9283 is the α4β2 nicotinic acetylcholine receptor (nAChR), specifically the 3α:2β stoichiometry. It acts as a positive allosteric modulator (PAM) of these receptors, selectively increasing the potency of acetylcholine at the 3α:2β receptors without modulating current conducted by the 2α:3β receptors. NS9283 increases the potency of ACh-evoked currents approximately 60-fold without affecting the maximum efficacy in HEK293 cells expressing human α4β2 receptors. The compound also increases the potency of varenicline to activate and desensitize α4β2 nAChRs. By allosterically modulating α4β2 nAChRs, NS9283 enhances cholinergic neurotransmission.
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| ln Vitro |
In vitro, NS9283 is a potent PAM of α4β2 nAChRs. It selectively increases ACh potency at the 3α:2β receptors while it does not modulate current conducted by the 2α:3β receptors. The compound increases the potency of ACh-evoked currents approximately 60-fold without affecting the maximum efficacy in HEK293 cells expressing human α4β2 receptors. NS9283 also increases the potency of varenicline to activate and desensitize α4β2 nAChRs. The compound's activity is typically measured using electrophysiological recordings (e.g., patch-clamp, two-electrode voltage clamp) in cells expressing α4β2 nAChRs. In these assays, NS9283 is applied to cells, and the potentiation of ACh-evoked currents is measured.
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| ln Vivo |
In vivo, NS9283 has been studied for its potential therapeutic applications in a series of neurological conditions such as attention deficit hyperactivity disorder (ADHD), schizophrenia, Parkinson's disease, and Alzheimer's disease. By allosterically modulating α4β2 nAChRs, NS9283 enhances cholinergic neurotransmission, which is impaired in these disorders. NS9283 reduces ethanol consumption, suggesting that it may also have potential for the treatment of alcohol use disorders. While specific in vivo efficacy data for NS9283 in animal models of these conditions are not extensively detailed in the available literature, its mechanism of action and in vitro activity suggest that it would be effective in enhancing cognitive function and reducing ethanol consumption.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for NS9283 involve radioligand binding studies using cell membranes expressing α4β2 nAChRs of various stoichiometries. Competitive binding assays are performed using a radiolabeled nAChR ligand (e.g., [3H]epibatidine) to determine the compound's affinity for the receptor. Selectivity profiling against other nAChR subtypes (α3β4, α7) and other neurotransmitter receptors is performed to assess the compound's specificity. Functional assays using electrophysiological recordings in cells expressing α4β2 nAChRs are employed to assess the compound's ability to potentiate ACh-evoked currents and to determine its PAM activity.
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| Cell Assay |
In vitro cellular assays for NS9283 are conducted in cell lines expressing α4β2 nAChRs, such as HEK293 cells. Cells are treated with varying concentrations of NS9283, and receptor activation is assessed using electrophysiological recordings or calcium imaging. The compound's ability to potentiate ACh-evoked currents is quantified by measuring the increase in current amplitude or the shift in the ACh dose-response curve. These assays confirm that NS9283 engages its target in a cellular context and produces the expected enhancement of α4β2 nAChR activity.
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| Animal Protocol |
In vivo animal studies for NS9283 would typically be conducted in animal models of cognitive impairment, ADHD, schizophrenia, Parkinson's disease, Alzheimer's disease, or alcohol use disorders. Animals would be administered the compound, and outcomes would be assessed based on the specific disease model. For example, in models of cognitive impairment, the compound's effects on learning and memory could be assessed using the Morris water maze or novel object recognition test. In models of alcohol use disorders, the compound's effects on ethanol consumption could be assessed using two-bottle choice or operant self-administration paradigms. These studies would confirm that NS9283 is effective in vivo and provide information about its therapeutic potential.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NS9283 indicate that it has a molecular weight of 248.24 and a molecular formula of C14H8N4O. The compound is a small molecule with drug-like physicochemical properties, including a molecular weight below 500 Da, which is generally considered favorable for oral bioavailability. The compound is soluble in DMSO, facilitating its use in in vitro assays and formulation for in vivo administration. For storage, the powder should be kept under appropriate conditions to maintain stability.
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| Toxicity/Toxicokinetics |
The toxicological profile of NS9283 is primarily derived from its use as a research compound in preclinical studies. As a PAM of α4β2 nAChRs, potential on-target effects could include changes in cognition, attention, and reward processing, given the roles of these receptors in these processes. The compound's selectivity for the 3α:2β stoichiometry may reduce the risk of off-target effects compared to non-selective nAChR modulators. Comprehensive toxicology studies would be required for therapeutic development, including assessments of neurological, cognitive, and behavioral function.
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| References | |
| Additional Infomation |
NS9283 is a potent, positive allosteric modulator of α4β2 nAChRs, acting selectively at the 3α:2β stoichiometry. It increases the potency of ACh-evoked currents approximately 60-fold without affecting the maximum efficacy. NS9283 also increases the potency of varenicline to activate and desensitize α4β2 nAChRs. The compound reduces ethanol consumption and has potential for the treatment of ADHD, schizophrenia, Parkinson's disease, and Alzheimer's disease. NS9283 is not approved for clinical use and is available from research chemical suppliers for preclinical studies.
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| Molecular Formula |
C14H8N4O
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|---|---|
| Molecular Weight |
248.25
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| Exact Mass |
248.07
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| Elemental Analysis |
C, 67.74; H, 3.25; N, 22.57; O, 6.44
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| CAS # |
913830-15-6
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| PubChem CID |
11998180
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| Appearance |
White to off-white solid powder
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| Density |
1.37±0.1 g/cm3(20 °C , 760mmHg)
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| Boiling Point |
469.9±55.0 °C (760 mmHg)
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| LogP |
2.67
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
353
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N#CC1C=C(C2ON=C(C3C=CC=NC=3)N=2)C=CC=1
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| InChi Key |
HGFXDSQLRSWUBO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H8N4O/c15-8-10-3-1-4-11(7-10)14-17-13(18-19-14)12-5-2-6-16-9-12/h1-7,9H
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| Chemical Name |
3-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)benzonitrile
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| Synonyms |
NS-9283; NS 9283; NS9283
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~16.67 mg/mL (~67.15 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0282 mL | 20.1410 mL | 40.2820 mL | |
| 5 mM | 0.8056 mL | 4.0282 mL | 8.0564 mL | |
| 10 mM | 0.4028 mL | 2.0141 mL | 4.0282 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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