| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
NOX2 1.9 μM (IC50) NOX4 2.47 μM (IC50)
NADPH oxidase 2 (NOX2, IC50 = 1.9 microM) and NADPH oxidase 4 (NOX4, IC50 = 2.47 microM). It is an orally active, BBB-penetrant small-molecule inhibitor of these NOX isoforms. |
|---|---|
| ln Vitro |
By using the parallel artificial membrane permeability assay (PAMPA), NADPH oxidase-IN-1 (compound 11) has a Pe value of 13.6 (10-6 cm/s) which indicates that it can cross the blood-brain barrier [1]. In BV2 microglia, LPS-induced ROS production is inhibited in a dose-dependent manner by NADPH oxidase-IN-1 (1 nM-10 mM; 30min) [1]. In BV2 cells, pro-inflammatory cytokine mRNA expression is inhibited by NADPH oxidase-IN-1 (10 μM; 24 h) [1]. Additionally, BV2 cell activation and migration are inhibited by NADPH oxidase-IN-1 (1 nM-10 mM; 24 h) [1].
NADPH oxidase-IN-1 inhibits NOX2 and NOX4 with IC50 values of 1.9 microM and 2.47 microM, respectively. It effectively suppresses the production of pro-inflammatory cytokines and reduces LPS-mediated microglial migration in vitro, indicating its potential to dampen neuroinflammatory responses. |
| ln Vivo |
In a mouse model of Parkinson's disease, NADPH oxidase-IN-1 (Compound 11) (30 mg/kg; po; daily for 4 weeks) reduces dopaminergic neuron loss and attenuates MPTP-induced microglial activation [1]. When given by intravenous injection (10-300 mg/kg; single dosage) or gavage (10-1000 mg/kg; single dose), NADPH oxidase-IN-1 is safe for both male and female mice [1]. Rat pharmacokinetic characteristics: Parameters C0 (μg/mL), Cmax (μg/mL), t1/2 (h), Tmax (h), AUClast (μg/h/mL) ke (1/h), Vd (L) Vd/F (L), Cl (L/h) Cl/F (L/h) F (%) IV (2 mg/kg) 1.70 0.79 0.468 1.32 0.211 0.217 PO (10 mg/kg) 0.609 5.01 [0.083-2] 1.31 0.170 1.99 0.341 56.0 PO (20 mg/kg) 0.783 6.13 [0.67-2] 4.16 0.159 1.82 0.217 88.9
In vivo, NADPH oxidase-IN-1 is orally active and can cross the blood-brain barrier (BBB). It has demonstrated in vivo efficacy in a mouse model of Parkinson's disease (PD), a disease characterized by neuroinflammation and oxidative stress. The compound has been shown to be safe in both male and female mice following intravenous injection (10-300 mg/kg) and oral gavage (10-1000 mg/kg) in single-dose studies. |
| Enzyme Assay |
For non-cellular assays, the activity of NOX2 and NOX4 can be measured in cell-free systems using recombinant enzymes. NADPH oxidase-IN-1 is added at varying concentrations (0.1-100 microM). The production of superoxide is measured by the reduction of cytochrome c or by a luminescence-based method (e.g., lucigenin chemiluminescence). IC50 values for each isoform are calculated from the resulting dose-response curves.
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| Cell Assay |
RT-PCR[1]
Cell Types: BV2 microglial cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited the mRNA expression of pro-inflammatory cytokines (iNOS, IL-1β, TNFα) in BV2 cells. Cell Migration Assay [1] Cell Types: BV2 microglial cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Ameliorated inflammatory response and migration of microglia. For cell-based assays, primary microglia or microglial cell lines (e.g., BV-2) are pre-incubated with NADPH oxidase-IN-1 (1-20 microM) for 1-2 hours. The cells are then stimulated with lipopolysaccharide (LPS) to induce an inflammatory response. The levels of pro-inflammatory cytokines (e.g., TNF-alpha, IL-6, IL-1beta) in the culture supernatant are measured by ELISA. Microglial migration is assessed using a Boyden chamber assay. The production of reactive oxygen species (ROS) is measured using a fluorescent probe such as DCFH-DA. |
| Animal Protocol |
For animal studies, NADPH oxidase-IN-1 can be administered orally to mouse models of Parkinson's disease (e.g., the MPTP-induced model or the alpha-synuclein overexpression model). Doses are typically in the range of 10-50 mg/kg, given daily for 1-4 weeks. Motor function is assessed by behavioral tests such as the rotarod test, open field test, and pole test. At the end of the study, brain tissue is harvested to measure the levels of oxidative stress markers (e.g., ROS, malondialdehyde), inflammatory cytokines (by ELISA or qPCR), and tyrosine hydroxylase (TH) expression as a marker of dopaminergic neuron survival.
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| ADME/Pharmacokinetics |
NADPH oxidase-IN-1 is orally bioavailable. It can be formulated in a vehicle such as 0.5% methylcellulose or a mixture of DMSO/PEG300/Tween-80/saline for oral gavage. The compound is small and able to cross the blood-brain barrier, reaching its targets in the central nervous system. Detailed pharmacokinetic parameters such as half-life (t1/2), Cmax, AUC, and oral bioavailability are available in the primary literature but were not detailed in the search results.
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| Toxicity/Toxicokinetics |
NADPH oxidase-IN-1 has been reported to be safe in both male and female mice following IV injection (10-300 mg/kg) and oral gavage (10-1000 mg/kg) in single-dose toxicity studies. These data suggest a favorable safety margin. No other specific toxicological data are available. As with any research chemical, standard safety precautions (gloves, lab coat, eye protection) should be used.
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| References | |
| Additional Infomation |
NADPH oxidase-IN-1 (CAS 2762405-17-2) is a research compound that has been developed for the study of neuroinflammation and oxidative stress. It is not an approved drug. The compound is also known as a NOX2/4 inhibitor with BBB-penetrant properties. It is a valuable tool for studying the role of NOX enzymes in Parkinson's disease and other neurological disorders, such as Alzheimer's disease, multiple sclerosis, and stroke.
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| Molecular Formula |
C20H27N3O2S
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|---|---|
| Molecular Weight |
373.51
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| Exact Mass |
373.182
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| CAS # |
2762405-17-2
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| PubChem CID |
166176935
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| Appearance |
Orange to red 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 |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
26
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| Complexity |
551
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1/C(/N(C(N1C1CCCCC1)=S)C)=C\C1C=CC(=CC=1)N(C)CCO
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| InChi Key |
ZRIXYNJXSCQFPE-NBVRZTHBSA-N
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| InChi Code |
InChI=1S/C20H27N3O2S/c1-21(12-13-24)16-10-8-15(9-11-16)14-18-19(25)23(20(26)22(18)2)17-6-4-3-5-7-17/h8-11,14,17,24H,3-7,12-13H2,1-2H3/b18-14+
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| Chemical Name |
(5E)-3-cyclohexyl-5-[[4-[2-hydroxyethyl(methyl)amino]phenyl]methylidene]-1-methyl-2-sulfanylideneimidazolidin-4-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 (167.33 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 | 2.6773 mL | 13.3865 mL | 26.7730 mL | |
| 5 mM | 0.5355 mL | 2.6773 mL | 5.3546 mL | |
| 10 mM | 0.2677 mL | 1.3387 mL | 2.6773 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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