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| Targets |
The primary target of (R)-alpha7 nAchR-JAK2-STAT3 agonist 1 is the alpha7 subunit of the nicotinic acetylcholine receptor (alpha7 nAChR). Upon binding to this ionotropic receptor on the surface of immune cells (like macrophages), it triggers a signaling cascade that involves the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), which then translocates to the nucleus to regulate gene expression.
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| ln Vitro |
(R)-alpha7 nAchR-JAK2-STAT3 agonist 1 effectively suppresses the expression of inducible nitric oxide synthase (iNOS), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in murine RAW264.7 macrophages. It potently inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) release, NF-kappaB activation, and the production of these pro-inflammatory cytokines, with an IC50 value of 0.32 uM for NO.
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| ln Vivo |
The compound is described as being used in the research of sepsis, which suggests its utility in animal models of this life-threatening inflammatory condition. In a typical in vivo model, mice would be subjected to cecal ligation and puncture (CLP) or intraperitoneal injection of LPS to induce systemic inflammation. Administration of (R)-alpha7 nAchR-JAK2-STAT3 agonist 1 would then be expected to reduce serum levels of pro-inflammatory cytokines and improve survival rates.
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| Enzyme Assay |
A standard method to measure JAK2 phosphorylation (activation) is via Western blot. To confirm target engagement, cells (e.g., RAW264.7 macrophages) are stimulated with LPS (100 ng/mL) for 30 minutes to activate the pathway. Then, cells are treated with the agonist (0.1-10 uM) for another 30 minutes. The cells are lysed in RIPA buffer containing phosphatase inhibitors. Protein lysates are separated by SDS-PAGE, transferred to a PVDF membrane, and probed with a phospho-specific JAK2 (Tyr1007/1008) antibody. Total JAK2 is used as a loading control.
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| Cell Assay |
A standard cell-based anti-inflammatory assay: RAW264.7 mouse macrophages are seeded in 24-well plates (5×10⁵ cells/well). The next day, the cells are pre-treated with (R)-alpha7 nAchR-JAK2-STAT3 agonist 1 at various concentrations (0.001-100 uM) for 1 hour. Then, the cells are stimulated with 1 ug/mL lipopolysaccharide (LPS) for 24 hours. The culture medium is collected, and the concentrations of TNF-alpha, IL-1beta, and IL-6 are measured using commercially available ELISA kits. To measure NO production, 50 uL of culture medium is mixed with an equal volume of Griess reagent and incubated at room temperature for 10 minutes, then the absorbance at 540 nm is read.
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| Animal Protocol |
A typical in vivo model for sepsis: Male BALB/c mice (8-10 weeks old, weighing 20-25 g) are administered (R)-alpha7 nAchR-JAK2-STAT3 agonist 1 (e.g., 0.1, 0.5, 1 mg/kg) intraperitoneally 30 minutes before a lethal or sub-lethal dose (e.g., 20 mg/kg) of LPS. Blood is collected at 2, 6, 12, and 24 hours post-LPS injection. Serum levels of TNF-alpha, IL-1beta, and IL-6 are measured by ELISA. Survival is monitored for 72 hours post-LPS challenge, and the survival curves are compared using the Mantel-Cox log-rank test.
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| ADME/Pharmacokinetics |
No PK data was found for (R)-alpha7 nAchR-JAK2-STAT3 agonist 1. As a small-molecule agonist, it is likely to be well-absorbed and distributed. Its ability to cross the blood-brain barrier (a property of many nAChR ligands) is not described. The half-life in rodents is likely on the order of hours.
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| Toxicity/Toxicokinetics |
No toxicity data was found for (R)-alpha7 nAchR-JAK2-STAT3 agonist 1. As an agonist of the alpha7 nAchR, which is present in the central nervous system and on immune cells, potential toxicities could include off-target activation of other nAChR subunits and CNS-related side effects. Standard toxicology studies would be required before any clinical development.
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| References | |
| Additional Infomation |
(R)-alpha7 nAchR-JAK2-STAT3 agonist 1 is a research-grade chemical. It is the R-enantiomer of the racemic agonist and is used to study the cholinergic anti-inflammatory pathway. This product is intended for laboratory research use only and is not for human therapeutic applications. It is a valuable tool for studying inflammation, sepsis, and the role of the JAK-STAT signaling pathway in immune regulation. Each product in one row, fields tab-separated.
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| Molecular Formula |
C25H30O6
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| Molecular Weight |
426.50
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| Related CAS # |
α7 nAchR-JAK2-STAT3 agonist 1;2108714-20-9
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| Appearance |
Typically exists as solids at room temperature
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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 | 2.3447 mL | 11.7233 mL | 23.4467 mL | |
| 5 mM | 0.4689 mL | 2.3447 mL | 4.6893 mL | |
| 10 mM | 0.2345 mL | 1.1723 mL | 2.3447 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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