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    A-438079 HCl
    A-438079 HCl

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1305
    CAS #: 899431-18-6Purity ≥98%

    Description: A-438079 HCl (A438079; A 438079), the hydrochloride salt of -438079, is a novel, potent, and selective P2X7 receptor antagonist with anti-Parkinson's disease effects. It inhibits P2X7 receptor with a pIC50 of 6.9. A438079 protects against acetaminophen-induced liver injury by inhibiting p450 isoenzymes, not by inflammasome activation. A-438079 reduced electrographic and clinical seizure severity during status epilepticus and reduced seizure-induced neuronal death in the neocortex. Blockade of P2X(7) receptors may represent a novel protective strategy for striatal DA terminals in Parkinson's disease.

    References: Neuroscience. 2007 Jun 8;146(4):1817-28; CNS Neurosci Ther. 2014 Jun;20(6):556-64.

    Related CAS#: 899507-36-9 (free base)

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    Molecular Weight (MW)342.61
    CAS No.899431-18-6  (HCl); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 61 mg/mL (178.0 mM)
    Water: 61 mg/mL (178.0 mM)
    Ethanol: 20 mg/mL warmed (58.4 mM)
    Solubility (In vivo)Saline: 30mg/mL  
    SynonymsA-438079; A 438079; A438079; A-438079 HCl.

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    In Vitro

    In vitro activity: 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.

    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. 

    In VivoIntraperitoneal 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). A-438079 partially but significantly prevents the 6-OHDA-induced depletion of striatal DA stores. Pretreatment with A-438079 reduces nociceptive behaviour scores in the HC model. 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.  
    Animal modelSprague-Dawley male rats 
    Formulation & DosageDissolved in Saline; 30 mg/kg; i.p.
    ReferencesNeuroscience. 2007 Jun 8;146(4):1817-28; CNS Neurosci Ther. 2014 Jun;20(6):556-64.

    These protocols are for reference only. InvivoChem does not independently validate these methods.

    A-438079 HCl
    A-438079 suppresses neonatal status epilepticus (SE). CNS Neurosci Ther. 2014 Jun;20(6):556-64. 
    A-438079 HCl
    Effects of A-438079 on hippocampal injury after neonatal status epilepticus (SE). CNS Neurosci Ther. 2014 Jun;20(6):556-64.  
    A-438079 HCl
    Comparison of A-438079 with phenobarbital and bumetanide. CNS Neurosci Ther. 2014 Jun;20(6):556-64.


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