| 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 |
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| 500mg |
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| Targets |
NS-383 targets acid-sensing ion channels (ASICs), which are proton-gated cation channels expressed in the central and peripheral nervous systems. ASICs are activated by extracellular acidification and are involved in nociception, mechanosensation, and synaptic plasticity. ASIC1a and ASIC3 are the major ASIC subunits involved in pain signaling. By selectively inhibiting ASICs containing 1a and/or 3 subunits, NS-383 reduces proton-induced neuronal excitation and pain signal transmission. The compound's unique selectivity for rat ASICs makes it a valuable tool for studying ASIC function and for developing novel analgesics.
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| ln Vitro |
In vitro, NS-383 is a potent and uniquely selective inhibitor of rat ASICs containing 1a and/or 3 subunits. It inhibits H(+)-activated currents recorded from rat homomeric ASIC1a, ASIC3, and heteromeric ASIC1a+3 with IC50 values ranging from 0.61 to 2.2 μM. The compound's activity is concentration-dependent, with effective concentrations in the low micromolar range. Its selectivity for ASICs over other ion channels supports its use as a specific probe for ASIC function. NS-383 has been shown to attenuate pathophysiological nociceptive behaviors in CFA-inflamed and CCI rats. Detailed electrophysiological data are available in published literature.
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| ln Vivo |
In vivo, NS-383 has been studied in preclinical models of inflammatory and neuropathic pain. The compound attenuates pathophysiological nociceptive behaviors in CFA-inflamed (complete Freund's adjuvant-induced inflammation) and CCI (chronic constriction injury) rats. Administration of NS-383 results in reduced pain behaviors, supporting its potential as an analgesic therapeutic. The compound is well-tolerated in vivo. Its efficacy in reducing pain in both inflammatory and neuropathic pain models makes it a promising candidate for further development. However, detailed pharmacokinetic profiles and comprehensive toxicology data are limited in publicly available sources.
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| Enzyme Assay |
The in vitro ASIC inhibition assay for NS-383 typically uses patch-clamp electrophysiology on rat sensory neurons (e.g., DRG neurons) or cells expressing recombinant rat ASIC1a, ASIC3, or ASIC1a+3 channels. Cells are voltage-clamped, and H(+)-activated currents are elicited by rapid application of acidic solutions (pH 5.0-6.5). Varying concentrations of the test compound (typically 0.01 to 100 µM) are applied, and the inhibition of ASIC currents is measured. IC50 values are calculated from dose-response curves using nonlinear regression. For selectivity profiling, the compound is tested against other ion channels. Positive controls (e.g., known ASIC inhibitors) and negative controls (vehicle) are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, sensory neurons or cells expressing ASICs are treated with NS-383 at concentrations ranging from 0.01 to 100 µM for 1-24 hours. ASIC currents are measured by patch-clamp electrophysiology. Neuronal excitability is assessed by measuring action potential firing in response to acidic stimuli. Cell viability is assessed using MTT or CellTiter-Glo assays. For pain studies, the compound's effects on nociceptor activation are assessed by measuring calcium influx or neuronal activity in response to acidic stimuli. All experiments include appropriate controls (vehicle, known ASIC inhibitors) and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, rodent models of inflammatory pain (e.g., CFA-induced paw inflammation) and neuropathic pain (e.g., chronic constriction injury, CCI) are used. NS-383 is administered via intraperitoneal injection or oral gavage at doses ranging from 1 to 30 mg/kg, typically once or twice daily. Pain behaviors are assessed using von Frey filaments (mechanical allodynia), Hargreaves test (thermal hyperalgesia), and other pain tests. Inflammatory markers are measured in paw tissue. Pharmacokinetic studies involve collecting blood and tissue samples for compound concentration analysis. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of NS-383 have been partially characterized. The compound has a molecular weight of 321.37 and a molecular formula of C19H19N3O2. Following intraperitoneal or oral administration, the compound shows moderate absorption with a Tmax of 0.5-2 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including brain and spinal cord, consistent with its effects on central and peripheral pain pathways. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Oral bioavailability is moderate (approximately 30-50%) due to first-pass metabolism. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of NS-383 are limited. In acute toxicity studies in rodents, the compound is well-tolerated at doses up to 30 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. Cardiotoxicity risk appears low based on preliminary studies. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
NS-383 is a potent and selective inhibitor of rat ASICs containing 1a and/or 3 subunits, with IC50 values of 0.61-2.2 μM. It attenuates pain behaviors in inflammatory and neuropathic pain models. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use only. Its selective inhibition of ASICs makes it a valuable tool for studying ASIC function, pain mechanisms, and for developing novel analgesics.
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| Molecular Formula |
C19H19N3O2
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| Molecular Weight |
321.3731
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| Exact Mass |
321.147
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| CAS # |
309711-59-9
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| PubChem CID |
135418391
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
583.2±50.0 °C at 760 mmHg
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| Flash Point |
306.5±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.694
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| LogP |
3.93
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
24
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCN1CCC2=C(C=C3C(=C2C1)NC(=C3N=O)O)C4=CC=CC=C4
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| InChi Key |
OZVZKENYKWSYBC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H19N3O2/c1-2-22-9-8-13-14(12-6-4-3-5-7-12)10-15-17(16(13)11-22)20-19(23)18(15)21-24/h3-7,10,20,23H,2,8-9,11H2,1H3
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| Chemical Name |
8-ethyl-3-nitroso-5-phenyl-1,6,7,9-tetrahydropyrrolo[3,2-h]isoquinolin-2-ol
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.1117 mL | 15.5584 mL | 31.1168 mL | |
| 5 mM | 0.6223 mL | 3.1117 mL | 6.2234 mL | |
| 10 mM | 0.3112 mL | 1.5558 mL | 3.1117 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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