899431-18-6
899431-18-6 structure
- Name: A 438079 hydrochloride
- Chemical Name: A-438079 (hydrochloride)
- CAS Number: 899431-18-6
- Molecular Formula: C13H10Cl3N5
- Molecular Weight: 342.611
- Catalog: Signaling Pathways Membrane Transporter/Ion Channel P2X Receptor
- Create Date: 2017-07-19 02:27:49
- Modify Date: 2024-01-09 17:36:30
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A 438079 (hydrochloride) is a potent, and selective P2X7 receptor antagonist with pIC50 of 6.9.
| Name | A-438079 (hydrochloride) |
|---|---|
| Synonyms |
3-{[5-(2,3-Dichlorophenyl)-1H-tetrazol-1-yl]methyl}pyridine hydrochloride (1:1)
Pyridine, 3-[[5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl]methyl]-, hydrochloride (1:1) A 438079 (hydrochloride) |
| Description | A 438079 (hydrochloride) is a potent, and selective P2X7 receptor antagonist with pIC50 of 6.9. |
|---|---|
| Related Catalog | |
| Target |
pIC50: 6.9 |
| In Vitro | In 1321N1 cells stably expressing rat P2X7 receptors, A 438079 blocks BzATP-(10 μM) evoked changes in intracellular calcium concentrations with an IC50 of 321 nM. A 438079 is also selective for the P2X7 receptor, at concentrations up to 100 μM[1]. |
| In Vivo | A 438079 (80 μmol/kg, i.v.) reduces noxious and innocuous evoked activity of different classes of spinal neurons in neuropathic rats. A 438079 (100 and 300 μmol/kg, i.p.) significantly raises withdrawal thresh-olds in both the SNL and CCI models[1]. Intraperitoneal injection of A 438079 (5 and 15 mg/kg) 60 min after triggering seizures reduces seizure severity and neuronal death within the hippocampus. A 438079 has superior neuroprotective effects compared with an equally dose of phenobarbital (25 mg/kg)[2]. A 438079 partially but significantly prevents the 6-OHDA-induced depletion of striatal DA stores[3]. Pretreatment with A 438079 reduces nociceptive behaviour scores in the HC model[4]. |
| Kinase Assay | 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 Admin | 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 |
[2]. Mesuret G, et al. CNS Neurosci Ther. 2014 Jun;20(6):556-64. |
| Molecular Formula | C13H10Cl3N5 |
|---|---|
| Molecular Weight | 342.611 |
| Exact Mass | 341.000183 |
| PSA | 56.49000 |
| LogP | 3.89220 |
| Storage condition | -20℃ |