| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
P2X7 Receptor 6.9-7.2 (pIC50)
The primary target of GW791343 trihydrochloride is the human P2X7 receptor (hP2X7), an ATP-gated ion channel that plays a crucial role in inflammasome activation, cytokine release, and cell death. GW791343 acts as a negative allosteric modulator, meaning it binds to a site distinct from the ATP-binding orthosteric site and inhibits receptor function in a non-competitive manner. It exhibits species-specific activity, acting as a NAM on the human P2X7 receptor with a pIC50 of 6.9-7.2, while showing different or no activity on P2X7 receptors from other species. This selectivity makes it a valuable tool for studying human P2X7 receptor biology. |
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| ln Vitro |
GW791343 trihydrochloride (0.01, 0.03, 0.1, 0.3, 1, 3, 10 µM; 40 min) has antagonistic action that is non-competitive towards the human P2X7 receptor[1]. The human P2X7 receptor exhibits an anegative allosteric modulator activity in response to GW791343 trihydrochloride (3, 10, 30 µM; 40 min)[1]. The ATP rhythm in SCN cells is improved by GW791343 trihydrochloride (5 µM; 24-48 h; ATP measured every 4 h)[2].
In vitro, GW791343 trihydrochloride potently inhibits agonist-stimulated responses in cells expressing the human P2X7 receptor. In functional assays using HEK293 cells expressing recombinant human P2X7, the compound inhibits agonist-stimulated ethidium accumulation, a measure of P2X7-mediated pore formation, in both sucrose and NaCl buffers. The compound demonstrates its activity with a pIC50 range of 6.9-7.2. It has been shown to inhibit P2X7-mediated calcium influx and subsequent downstream signaling events. GW791343 trihydrochloride is typically tested at concentrations of 3, 10, and 30 µM with a 40-minute incubation period in cellular assays. It is soluble in DMSO and is used as a research tool to study P2X7 receptor function and pharmacology. |
| ln Vivo |
In vivo, GW791343 trihydrochloride has been investigated for its potential in treating neurological disorders by modulating P2X7 receptor activity. Studies have shown that GW791343 trihydrochloride enhances circadian ATP release, suggesting a role in regulating biological rhythms. By acting as a negative allosteric modulator of the P2X7 receptor, it can potentially attenuate neuroinflammation and excitotoxicity in various disease models. The compound's ability to penetrate the central nervous system and modulate P2X7-dependent signaling pathways positions it as a valuable pharmacological tool for studying the therapeutic potential of P2X7 inhibition in conditions such as chronic pain, depression, and neurodegenerative diseases.
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| Enzyme Assay |
The in vitro binding and functional characterization of GW791343 trihydrochloride typically involves the use of HEK293 cells stably or transiently expressing recombinant human P2X7 receptors. For receptor binding studies, radioligand binding assays using [3H]- or [35S]-labeled ATP analogs can be performed to assess the compound's allosteric modulation of orthosteric ligand binding. Functional assays measure the inhibition of agonist-stimulated responses, such as ethidium accumulation or calcium influx. Cells are pre-incubated with the compound for 10-40 minutes prior to agonist stimulation, and the inhibition of the response is measured to determine the pIC50 value.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: HEK293 cells (expressing human recombinant P2X7 receptors). Tested Concentrations: 0.01, 0.03, 0.1, 0.3, 1, 3, 10 µM. Incubation Duration: 40 min (pre-incubate for 10 min and incubate with other P2X7 receptor antagonists for another 30 min). Experimental Results: Inhibited agonist-stimulated ethidium accumulation in both sucrose and NaCl buffer. diminished maximal responses toATP and BzATP in sucrose buffer. Cell Viability Assay[1] Cell Types: HEK293 cells (expressing human recombinant P2X7 receptors). Tested Concentrations: 3 , 10, 30 µM. Incubation Duration: 40 min (pre-incubate for 10 min and incubate with other P2X7 receptor antagonists for another 30 min). Experimental Results: demonstrated slow reversal effects at the human P2X7 receptor (after 45 min had reversed sufficiently) , and had a rapid dissociation rate. Cell Viability Assay[2] Cell Types: SCN cells (from 16-to 21- day-old Wistar rats, which are kept under a controlled 12-12 h light-dark cycle from birth). Tested Concentrations: 5 µM (replace the medium Cellular assays for GW791343 trihydrochloride are typically performed using HEK293 cells that have been transfected to express the human recombinant P2X7 receptor. The protocol involves pre-incubating cells with various concentrations of GW791343 (typically ranging from 3 to 30 µM) for approximately 10 minutes. Following this pre-incubation, cells are stimulated with a P2X7 receptor agonist (such as BzATP or ATP) in the presence of the compound for an additional 30 minutes. Functional readouts include the measurement of agonist-stimulated ethidium accumulation, calcium mobilization, or the release of cytokines like IL-1β or IL-18. The compound's inhibitory effect is quantified by comparing the response in treated cells versus control cells. |
| Animal Protocol |
In vivo animal studies for GW791343 trihydrochloride typically involve the administration of the compound to rodent models of neurological or inflammatory diseases. The compound is often administered via intraperitoneal (i.p.) injection or oral gavage at doses determined from pharmacokinetic studies. Given its ability to enhance circadian ATP release, studies may investigate its effects on circadian rhythms by monitoring locomotor activity or clock gene expression. In models of neuroinflammation, endpoints such as cytokine levels in the brain, microglial activation, and behavioral outcomes (e.g., pain sensitivity, depressive-like behaviors) are assessed. The compound's ability to penetrate the blood-brain barrier and modulate P2X7-dependent pathways in the central nervous system is a key focus of these studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GW791343 trihydrochloride are not extensively detailed in the available literature. However, as a small molecule with a molecular weight of approximately 562.2 g/mol (free base), its properties are typical of allosteric modulators. The compound is supplied as a solid and is soluble in DMSO, indicating moderate lipophilicity that may facilitate oral absorption and central nervous system penetration. For research purposes, it is typically stored as a powder at -20°C for up to three years or in solution at -80°C for up to six months. Detailed parameters such as half-life, volume of distribution, and bioavailability are not publicly available and would need to be determined experimentally.
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| Toxicity/Toxicokinetics |
There is no specific toxicity data reported for GW791343 trihydrochloride in the available literature. As a research chemical intended for laboratory use only, it should be handled with standard safety precautions, including the use of appropriate personal protective equipment such as gloves and safety goggles. The compound is not approved for human therapeutic use, and any potential toxicity would need to be assessed through formal toxicological studies if it were to be developed further. Researchers should consult the material safety data sheet (MSDS) for detailed safety and handling information.
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| References | |
| Additional Infomation |
GW791343 trihydrochloride (GW791343 3HCl) is a human P2X7 receptor negative allosteric modulator with a pIC50 of 6.9-7.2. It exhibits species-specific activity and enhances circadian ATP release. The compound is used in neurological disease research. It is available as a trihydrochloride salt with a purity of ≥98%. GW791343 trihydrochloride is a valuable tool for studying the role of the P2X7 receptor in neuroinflammation, pain, and circadian biology, and its mechanism of action as a negative allosteric modulator provides a distinct pharmacological profile compared to orthosteric antagonists.
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| Molecular Formula |
C20H27CL3F2N4O
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|---|---|
| Molecular Weight |
483.810388803482
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| Exact Mass |
482.122
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| CAS # |
309712-55-8
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| Related CAS # |
GW791343 dihydrochloride;1019779-04-4
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| PubChem CID |
9848159
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
6.124
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=CC(CN2CCNCC2)=CC=C1C)(=O)CNC1=CC=C(F)C(F)=C1.[H]Cl.[H]Cl.[H]Cl
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| InChi Key |
WSBRAHWNJBXXJM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H24F2N4O.3ClH/c1-14-2-3-15(13-26-8-6-23-7-9-26)10-19(14)25-20(27)12-24-16-4-5-17(21)18(22)11-16;;;/h2-5,10-11,23-24H,6-9,12-13H2,1H3,(H,25,27);3*1H
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| Chemical Name |
2-(3,4-difluoroanilino)-N-[2-methyl-5-(piperazin-1-ylmethyl)phenyl]acetamide;trihydrochloride
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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 | 2.0669 mL | 10.3346 mL | 20.6693 mL | |
| 5 mM | 0.4134 mL | 2.0669 mL | 4.1339 mL | |
| 10 mM | 0.2067 mL | 1.0335 mL | 2.0669 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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