A 438079 hydrochloride

• CAT Number: I005381
• CAS Number: 899431-18-6
• Molecular Formula: C13H9Cl2N5 • HCl
• Molecular Weight: 342.6
• Purity: ≥95%
• Synonyms: 3-[[5-(2,3-dichlorophenyl)tetrazol-1-yl]methyl]pyridine;hydrochloride
• Target: P2X Receptor
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• InChIKey: MBTJFFMIPPMRGR-UHFFFAOYSA-N

A 438079 Hcl is a competitive P2X7 receptor antagonist (pIC50 = 6.9 for the inhibition of Ca2+ influx in the human recombinant P2X7 cell line).IC50 Value:The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia[1]. The P2X7 receptor participates in purinergic signaling, which may promote the progression of ADPKD[3].in vitro:. To determine the effect of inhibiting P2X7Rs on hippocampal inflammatory cytokine production, the expression levels of three cytokines, IL-1, TNF-α and IL-6 were tested by RT-PCR at +3D. As expected, transient global cerebral I/R significantly increased mRNA expression of IL-1, TNF-α and IL-6 in the hippocampus. Administration of BBG 10 μg, OxATP 1 μg or A-438079 3 μg markedly attenuated the I/R-induced overexpression of IL-1, TNF-α and IL-6[2].in vivo: Neuronal survival in A-438079 treated animals was similar to survival rates in those treated with BBG and A-438079 0.3 μg and A-438079 3 μg treated animals, with significantly more surviving hippocampal CA1 neurons when compared to the A-438079 0.03 μg and saline groups. Rats from the A-438079 3 μg group had higher neuron survival rates than those from the OxATP 1 μg group (87.8 ± 6.0% versus70.4 ± 8.6%). The neuron survival rate in the BBG 10 μg and A-438079 3 μg group did not differ from each other at +7D. The survival rates of rats during the seven days after I/R injury was significantly reduced in the BBG 10 μg (95.2%), OxATP 1 μg(92.0%) and A-438079 3 μg (93.8%) treated groups when compared to the saline group(72.4%). No significant difference was observed among the BBG 10 μg, OxATP 1 μg and A-438079 3 μg group[2].Clinical trial: N/A

Reference

[1]. Gadeock S, Pupovac A, Sluyter V, P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells. Purinergic Signal. 2012 Dec;8(4):669-76.
[2]. Ketan Chu, Bo Yin, Jingye Wang, Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus. J Neuroinflammation. 2012; 9: 69.
[3]. Chang MY, Lu JK, Tian YC, Inhibition of the P2X7 receptor reduces cystogenesis in PKD. J Am Soc Nephrol. 2011 Sep;22(9):1696-706.