| CAS |
899431-18-6 |
| Chinese Name |
A-438079盐酸盐 |
| English Name |
A-438079 Hydrochloride |
| Synonyms |
3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶单盐酸盐 |
| Molecular Formula |
C13H10Cl3N5 |
| Molecular Weight |
342.61 |
| Solubility |
Soluble in Water/DMSO ≥10mg/mL |
| Purity |
≥98% |
| Appearance |
White to off-white Solid |
| Storage |
Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| EC |
EINECS 604-604-1 |
| MDL |
MFCD09971142 |
| SMILES |
ClC1=C(Cl)C(C2=NN=NN2CC3=CC=CN=C3)=CC=C1.[H]Cl |
| Target Point |
P2X Receptor |
| Passage |
Membrane Transporter&Ion Channel |
| Background |
A-438079 Hydrochloride is a potent and selective P2X7 receptor antagonist. |
| Biological Activity |
A 438079 (hydrochloride) is a potent， and selective P2X7 receptor antagonist[1] |
| 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.)signi cantly 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 signi cantly prevents the 6-OHDA-induced depletion of striatal DA stores[3]. Pretreatment with A 438079 reduces nociceptive behaviour scores in the HC model[4]. |
| 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.[2] |
| 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 uorescence 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 t.[1] |
| Data Literature Source |
[1]. McGaraughty S，et al. P2X7-related modulation of pathological nociception in rats. Neuroscience. 2007 Jun 8;146(4):1817-28.
[2]. Mesuret G，et al. CNS Neurosci Ther. 2014 Jun;20(6):556-64.
[3]. Marcellino D，et al. On the role of P2X(7) receptors in dopamine nerve cell degeneration in a rat model of Parkinson's disease: studies with the P2X(7) receptor antagonist A-438079. J Neural Transm (Vienna). 2010 Jun;117(6):681-7.
[4]. Martins JP，et al. The role of P2X7 purinergic receptors in inflammatory and nociceptive changes accompanying cyclophosphamide-induced haemorrhagic cystitis in mice. Br J Pharmacol. 2012 Jan;165(1):183-96. |
| Unit |
Bottle |
| Specification |
5mg |
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