A 438079 hydrochloride |
| Catalog No.GC13733 |
An antagonist of the nucleotide receptor P2X7
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 899431-18-6
Sample solution is provided at 25 µL, 10mM.
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A 438079 hydrochloride is a selective antagonist of P2X7 receptor with IC50 values of 100 and 300 nM in rat and human, respectively [1].
A 438079 is a derivative of the origin compound tetrazole 5 selected out as a novel P2X7 receptor antagonist. In human 1321N1 astrocytoma cells with expressing recombinant human P2X7, A 438079 treatment suppressed the Ca 2+ flux with pIC50 value of 6.9. In the pore formation assay, A 438079 blocked the pore formation of human THP-1 cells and prevented the cells from uptaking the diiodide dye YO-PRO. Moreover, in the spinal nerve ligation model, administration of A 438079 reduced the neuropathic pain induced by the application of a von Frey hair. The ED50 value was 76 μM/kg [2].
References:
1. Nelson D W, Gregg R J, Kort M E, et al. Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. Journal of medicinal chemistry, 2006, 49(12): 3659-3666.
2. Donnelly-Roberts D L, Jarvis M F. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. British journal of pharmacology, 2007, 151(5): 571-579.
Kinase experiment: | Human astrocytoma cells, 1321N1, are grown to stably express rat P2X7, human P2X4, P2X2a, P2X2/3, P2X1, P2Y1 and P2Y2 recombinant receptors. Agonist, BzATP, 2,3-O-(4-ben-zoylbenzoyl)-ATP or ATP-induced changes in intracellular Ca2+ concentrations are assessed in all of the cell lines using the Ca2+ chelating dye, Fluo-4, in conjunction with a Fluorometric Imaging Plate Reader. The cells are plated out the day before the experiment onto poly-D-lysine-coated black 96 well plates. After the agonist addition, changes in intracellular Ca2+ concentrations are recorded, per second, for 3 min. Ligands are tested at 11 half-log concentrations from 10-10 to 10-4 M. BzATP or ATP concentrations corresponds to the EC70 values for each receptor to enable comparison of antagonist potencies across the multiple P2 receptor subtypes. A 438079 is added to the cell plate and fluorescence data are collected for 3 min before the addition of agonist, subsequently, data are then collected for another 2 min. The pEC50 or pIC50 values are derived from a single curve fit. |
Animal experiment: | To confirm A 438079 reach the brain after systemic administration, P10 rat pups are injected with 5 mg/kg A 438079 and killed either 10 min, 30 min, or 2 h later (n=4 per group). Blood samples are centrifuged at 1000×g for 10 min to isolate the plasma. Samples are analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) by a service provider. Briefly, protein is precipitated from 50 μL aliquots of the individual plasma or brain tissue homogenate, and A 438079 is quantified by LC-MS/MS from a five-point standard curve. |
References: [1]. McGaraughty S, et al. P2X7-related modulation of pathological nociception in rats. Neuroscience. 2007 Jun 8;146(4):1817-28. | |
| Cas No. | 899431-18-6 | SDF | |
| Chemical Name | 3-[[5-(2,3-dichlorophenyl)tetrazol-1-yl]methyl]pyridine;hydrochloride | ||
| Canonical SMILES | C1=CC(=C(C(=C1)Cl)Cl)C2=NN=NN2CC3=CN=CC=C3.Cl | ||
| Formula | C13H10Cl3N5 | M.Wt | 342.61 |
| Solubility | ≥ 34.3 mg/mL in DMSO, ≥ 49.8 mg/mL in EtOH with ultrasonic and warming, ≥ 94 mg/mL in Water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.9188 mL | 14.5939 mL | 29.1877 mL |
| 5 mM | 583.8 μL | 2.9188 mL | 5.8375 mL |
| 10 mM | 291.9 μL | 1.4594 mL | 2.9188 mL |
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- Purity: >99.50%
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