A 438079
(Synonyms: 3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶) 目录号 : GC17212
A 438079是一种高选择性P2X7受体（P2X7R）拮抗剂，对大鼠P2X7R的IC50值为0.1μM。
Cas No.:899507-36-9
Sample solution is provided at 25 µL, 10mM.
A 438079 is a highly selective P2X7R antagonist, with an IC50 value of 0.1μM at rat P2X7R [1]. A 438079 can block P2X7R-mediated changes in intracellular calcium concentrations[2]. A 438079 has been widely used to inhibit liver fibrosis progression and inflammation in animal models[3].
In vitro, A 438079 treatment (10μM) for 72h significantly inhibited the invasion and migration of HCT-116 and SW620 cells and promoted apoptosis by regulating the Bcl-2/caspase9/caspase3 signaling pathway[4]. Treatment with 100μM A 438079 for 48 hours remarkably inhibited human dermal fibroblasts proliferation and reduced cell motility[5]. Treatment of LOVO cells with 10μM A 438079 for 2 hours significantly inhibited the ATP-induced proliferation of LOVO cells, and dramatically reduced the ATP-induced inward current and intracellular calcium concentration[6].
In vivo, A 438079 treatment at a single dose of 15mg/kg via intraperitoneal injection for 6h prevented lipopolysaccharide (LPS)-induced liver injury and serum AST and ALT enzyme activities in rats[7]. Daily intraperitoneal injection of A 438079 at a dose of 80mg/kg for 3 days attenuated lung injury induced by spinal cord injury and reduced alveolar type II cell apoptosis in mice[8]. Intraperitoneal injection of A 438079 (100μmol/kg/day) for 14 days suppressed corneal allograft rejection and reduced Th1/Th17 cell infiltration in the corneal grafts within the murine model of corneal allograft transplantation[9].
References:
[1] Donnelly‐Roberts D L, Jarvis M F. Discovery of P2X7 receptor‐selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states[J]. British journal of pharmacology, 2007, 151(5): 571-579.
[2] Donnelly‐Roberts D L, Namovic M T, Han P, et al. Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors[J]. British journal of pharmacology, 2009, 157(7): 1203-1214.
[3] Huang C, Yu W E I, Cui H, et al. P2X7 blockade attenuates mouse liver fibrosis[J]. Molecular medicine reports, 2014, 9(1): 57-62.
[4] Zhang Y, Li F, Wang L, et al. A438079 affects colorectal cancer cell proliferation, migration, apoptosis, and pyroptosis by inhibiting the P2X7 receptor[J]. Biochemical and Biophysical Research Communications, 2021, 558: 147-153.
[5] Soszyńska M, Komorowski M, Łuszczyński K, et al. Differential Effect of P2X7 Receptors on Proliferation and Migration of Human Keratinocytes and Dermal Fibroblasts[J]. International Journal of Molecular Sciences, 2025, 26(17): 8548.
[6] Zhang W, Hu C, Luo H, et al. Activation of P2× 7 receptor promotes the invasion and migration of colon cancer cells via the STAT3 signaling[J]. Frontiers in Cell and Developmental Biology, 2020, 8: 586555.
[7] Kara A, Ozkanlar S. Blockade of P2X7 receptor‐mediated purinergic signaling with A438079 protects against LPS-induced liver injury in rats[J]. Journal of Biochemical and Molecular Toxicology, 2023, 37(10): e23443.
[8] Jiang W, Li M, He F, et al. Inhibition of NLRP3 inflammasome attenuates spinal cord injury‐induced lung injury in mice[J]. Journal of cellular physiology, 2019, 234(5): 6012-6022.
[9] Fan X, Zhang J, Dai Y, et al. Blockage of P2X7R suppresses Th1/Th17-mediated immune responses and corneal allograft rejection via inhibiting NLRP3 inflammasome activation[J]. Experimental Eye Research, 2021, 212: 108792.
A 438079是一种高选择性P2X7受体（P2X7R）拮抗剂，对大鼠P2X7R的IC50值为0.1μM[1]。该化合物可阻断P2X7R介导的细胞内钙浓度变化[2]。并广泛应用于动物模型中抑制肝纤维化进展和炎症反应[3]。
在体外，10μM A 438079处理72小时能显著抑制HCT-116和SW620细胞的侵袭与迁移，并通过调控Bcl-2/caspase9/caspase3信号通路促进凋亡[4]。100μM的A 438079处理人真皮成纤维细胞48小时可显著抑制细胞增殖并降低运动能力[5]。10μM的A 438079处理LOVO细胞2小时能抑制ATP诱导的细胞增殖，并显著降低ATP引发的内向电流和细胞内钙浓度[6]。
在体内，大鼠单次腹腔注射A 438079（15mg/kg；6小时）可预防脂多糖（LPS）诱导的肝损伤及血清AST和ALT酶活性升高[7]。小鼠每日腹腔注射80mg/kg剂量的A 438079（持续3天）能减轻脊髓损伤诱导的肺损伤并减少肺泡II型细胞凋亡[8]。小鼠角膜同种异体移植模型中每日腹腔注射A 438079（100μmol/kg/天；持续14天）可抑制角膜移植排斥反应，并减少移植物内Th1/Th17细胞浸润[9]。
| Cell experiment [1]: | |
Cell lines | HCT-116 cells |
Preparation Method | HCT-116 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS), 100μg/ml penicillin, and 100μg/ml streptomycin. Cells were seeded in 96-well plates at a density of approximately 2000 to 3000 cells/well. Subsequently, cells were cultured in medium containing different concentrations of A 438079 (0, 1, 10, 20, and 50μM). After 72h of incubation, 10μl of CCK-8 solution was added to each well, and the cells were incubated for an additional 2h at 37°C, and absorbance at 450nm was measured. |
Reaction Conditions | 0, 1, 10, 20, and 50μM; 72h |
Applications | A 438079 treatment significantly inhibited the proliferation of HCT-116 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley male rats |
Preparation Method | Thirty-six Sprague-Dawley male rats (weighing 200-220g) were randomly divided into 3 groups, each group was equal. All rats were maintained under standard laboratory conditions (12:12 light/dark cycle, 22 to 24°C, relative humidity 60%) and without restriction of water intake throughout the study period. Rats in control group without any treatment; Rats in LPS group were intraperitoneally injected with 8mg/kg LPS. Rats in LPS +A 438079 group were intraperitoneally injected with 8mg/kg LPS and 15mg/kg A 438079. All rats were anesthetized with 2.1% sevoflurane, and blood samples were collected from the rat heart 6h after the start of the study for continued analysis, followed by removal of liver tissue for histopathological analysis. |
Dosage form | 15mg/kg once for 6h; i.p. |
Applications | A 438079 treatment prevented LPS-induced liver injury and serum AST and ALT enzyme activities in rats. |
References: | |
| Cas No. | 899507-36-9 | SDF | |
| 别名 | 3-[[5-(2,3-二氯苯基)-1H-四唑-1-基]甲基]吡啶 | ||
| 化学名 | 3-[[5-(2,3-dichlorophenyl)tetrazol-1-yl]methyl]pyridine;hydrochloride | ||
| Canonical SMILES | C1=CC(=C(C(=C1)Cl)Cl)C2=NN=NN2CC3=CN=CC=C3.Cl | ||
| 分子式 | C13H9Cl2N5 | 分子量 | 306.15 |
| 溶解度 | DMSO : 100 mg/mL (326.64 mM; Need ultrasonic); H2O : 0.2 mg/mL (0.65 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.2664 mL | 16.3319 mL | 32.6637 mL |
| 5 mM | 653.3 μL | 3.2664 mL | 6.5327 mL |
| 10 mM | 326.6 μL | 1.6332 mL | 3.2664 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet