A 438079 HCl

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Chemical Structure| 899431-18-6 同义名 : A-438079 (hydrochloride);A 438079 hydrochloride
CAS号 : 899431-18-6
货号 : A152651
分子式 : C13H10Cl3N5
纯度 : 99%+
分子量 : 342.611
MDL号 : MFCD09971142
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(306.47 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 1 mg/mL(2.92 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • P2X receptor

    P2X7, pIC50:6.9
描述 ATP is a key neurotransmitter in this process of inducing and maintaining chronic pain. P2X7 is the glial ATP receptor modulating the pathological pain. A 438079 HCl can inhibits P2X7 with an IC50 of 321 nM in 1321N1 cells. In pharmacokinetic rats, treatment of 10 μM/kg showed low mean plasma and brain levels of the drug, suggesting 84% binding rate to plasma protein. In SNL and CCI rats, treatment of 100 and 300 μM/kg significantly improved withdrawal thresholds with the ED50 of 76 and 100μM/kg respectively without affecting rat rotarod performance. Treatment of 80 μM/kg this drug in SNL rats didn't affect the von Frey-related discharges of hmWDR and mWDR but was effective against high intensity stimulation. Such an treatment also attenuated the evoked responses of neurons to thermal stimulation and decreased the level of spontaneous firing. Besides, A 438079 HCl with concentration of 1 μM reduced the P2X7 receptor agonist in non-neuronal DRG cells. IL-1β release was also inhibited by 75.6% at concentration of 3 μM in a dose- dependent manner[1]. The drug also showed effect on seizure in P10 rat model with the dose range from 0.5 to 50 mg/kg in a dose-dependent manner. And seizure damage was also reduced at either 5 or 15 mg/kg as well as reduced TUNEL staining and decreasing score for neuronal damage. The plasma levels declined rapidly to 2.3 μg/mL within 10 min with the initial concentration of 5 mg/kg of A 438079 HCl in the model, which did not affect cell apoptosis at either 5 or 50 mg/kg[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HEK cells Function assay Activity at rat P2X7 receptor expressed in HEK cells assessed as effect on BzATP-induced ethidium uptake, IC50=0.31623 μM 19191585
HEK293 cells Function assay Antagonist activity at human recombinant P2X7 receptor expressed in HEK293 cells assessed as inhibition of benzoylbenzoic ATP-induced calcium production by FLIPR assay, IC50=0.12303 μM 21536435
human 1321N1 cells Function assay Antagonist activity at human P2X7 receptor expressed in human 1321N1 cells assessed as inhibition of calcium flux by FLIPR, IC50=0.12589 μM 16759108
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.92mL

0.58mL

0.29mL

14.59mL

2.92mL

1.46mL

29.19mL

5.84mL

2.92mL
参考文献

[1]McGaraughty S, Chu KL, et al. P2X7-related modulation of pathological nociception in rats. Neuroscience. 2007 Jun 8;146(4):1817-28.

[2]Mesuret G, Engel T, et al. P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage. CNS Neurosci Ther. 2014;20(6):556-64.

[3]Xie Y, Williams CD, et al. Purinergic receptor antagonist A438079 protects against acetaminophen-induced liver injury by inhibiting p450 isoenzymes, not by inflammasome activation. Toxicol Sci. 2013;131(1):325-35.

[4]Martins JP, Silva RB, et al. The role of P2X7 purinergic receptors in inflammatory and nociceptive changes accompanying cyclophosphamide-induced haemorrhagic cystitis in mice. Br J Pharmacol. 2012;165(1):183-96.

[5]Zhao H, Zhang X, et al. P2X7 Receptor Suppression Preserves Blood-Brain Barrier through Inhibiting RhoA Activation after Experimental Intracerebral Hemorrhage in Rats. Sci Rep. 2016.