AZD8797 is a selective, high-affinity small-molecule inhibitor of CX3CR1, with a Ki value of 7nM for rat CX3CR1 [1]. AZD8797 has been widely used to inhibit inflammatory responses in different animal models by binding to receptors at different sites of CX3CL1 to affect CX3CL1 interaction with CX3CR1[2].
In vitro, AZD8797 pretreatment (2mM) for 1 hour significantly decreased the expression levels of CX3CR1 and MMP13 in rat chondrocytes after 24h lipopolysaccharide (LPS) stimulation[3]. Co-treatment of 5μM AZD8797 with 5μM olaparib for 48 hours significantly inhibited Caov-3 cell colony formation and inhibited cell proliferation[4]. Treatment with 10μM AZD8797 for 12 hours resulted in down-regulation of 5-HTR2a expression and decreased phosphorylation of P65 and IκB proteins in PC-12 cells[5].
In vivo, AZD8797 treatment via intraperitoneal injection at a dose of 10mg/kg/day for 10 days reduced spleen mass and cardiac levels of CCL2 and IL-15, with an increase of IL-4 in the mice with acute Trypanosoma cruzi infection[6]. Daily intraperitoneal injection of AZD8797 at a dose of 80μg/kg/day for 10 days can enhance the early behavioral recovery, inhibit the activation of apoptosis, and reduce the inflammatory response in a rat spinal cord injury model[7]. AZD8797 (2mg/kg/day) administered via the tail vein for 5 days reduced proteinuria, cell proliferation, and inflammation of glomerulus in rats with mesangial proliferative glomerulonephritis (MsPGN)[8].
References:
[1] Ridderstad Wollberg A, Ericsson-Dahlstrand A, Juréus A, et al. Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis[J]. Proceedings of the National Academy of Sciences, 2014, 111(14): 5409-5414.
[2] Huang J M, Zhao N, Hao X N, et al. CX3CL1/CX3CR1 signaling mediated neuroglia activation is implicated in the retinal degeneration: a potential therapeutic target to prevent photoreceptor death[J]. Investigative Ophthalmology & Visual Science, 2024, 65(1): 29-29.
[3] Huang J, Zheng X, Meng J, et al. Experimental study on the role and biomarker potential of CX3CR1 in osteoarthritis[J]. Annals of medicine, 2025, 57(1): 2529577.
[4] Xie J, Barbolina M V. Dual Targeting of CX3CR1 and PARP in Models of High-Grade Serous Ovarian Carcinoma[J]. Cancers, 2024, 16(22): 3728.
[5] Pei J, Zou Y, Wan C, et al. CX3CR1 mediates motor dysfunction in mice through 5-HTR2a[J]. Behavioural brain research, 2024, 461: 114837.
[6] Pio S, Menezes T P, Louise V, et al. Role of the CX3CL1/CX3CR1 axis in iron metabolism and immune regulation during acute Trypanosoma cruzi infection[J]. Frontiers in Immunology, 2025, 16: 1585883.
[7] Chen G, Zhou Z, Sha W, et al. A novel CX3CR1 inhibitor AZD8797 facilitates early recovery of rat acute spinal cord injury by inhibiting inflammation and apoptosis[J]. International journal of molecular medicine, 2020, 45(5): 1373-1384.
[8] Zhang J, Fang Q, Huang Y, et al. CX3CR1+ Monocytes/Macrophages Promote Regional Immune Injury in Mesangial Proliferative Glomerulonephritis through Crosstalk with Activated Mesangial Cells[J]. Research, 2025, 8: 0716.
AZD8797是一种选择性高亲和力CX3CR1小分子抑制剂，对大鼠CX3CR1的Ki值为7nM[1]。AZD8797通过在不同位点与受体结合影响CX3CL1与CX3CR1的相互作用，已广泛应用于不同动物模型中抑制炎症反应[2]。
在体外，2mM的AZD8797预处理1小时可显著降低脂多糖（LPS）刺激24小时后大鼠软骨细胞中CX3CR1和MMP13的表达水平[3]。5μM的AZD8797与5μM奥拉帕利联合处理48小时能显著抑制Caov-3细胞集落形成和增殖[4]。10μM的AZD8797处理PC-12细胞12小时可下调5-HTR2a表达，并降低P65和IκB蛋白的磷酸化水平[5]。
在体内，急性克氏锥虫感染小鼠每日腹腔注射AZD8797（10mg/kg/day；持续10天）可减轻脾脏质量，降低心脏CCL2和IL-15水平，并增加IL-4[6]。脊髓损伤大鼠模型每日腹腔注射80μg/kg/day剂量的AZD8797（持续10天）能促进早期行为恢复，抑制细胞凋亡激活并减轻炎症反应[7]。系膜增生性肾小球肾炎（MsPGN）大鼠经尾静脉注射AZD8797（2mg/kg/day；持续5天）可减少蛋白尿、细胞增殖和肾小球炎症[8]。