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]。