R243 is a CCR8 receptor inhibitor that suppresses the signaling pathways triggered by CCL1, the endogenous ligand of CCR8[1-2]. R243 is primarily utilized in research related to immune and inflammatory diseases[3].
In vitro, treatment of mouse RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) with R243 (10µM) for 24 hours significantly inhibited CCL1-driven chemotactic migration in a CCL1-induced (10ng/mL) Transwell migration assay, although the inhibitory effect on the migration of human THP-1 monocytes was not significant [4]. When mouse peritoneal macrophages (PMφ) stimulated with LPS (100ng/mL) were treated with R243 (0–10µM) for 24 hours, R243 significantly suppressed the secretion of TNF-α, IL-6, and IL-10, and reduced the phosphorylation levels of the JNK and NF-κB signaling pathways[5].
In vivo, a peritoneal fibrosis mouse model, R243 (1.0mg/kg; administered via intraperitoneal injection three times a week for 28 days) significantly alleviated chlorhexidine gluconate-induced peritoneal inflammation and fibrosis by functionally inhibiting the CCR8 receptor. This was evidenced by reduced peritoneal thickness, decreased collagen deposition, and diminished macrophage infiltration[6]. In a thermal hyperalgesia test model, R243 (0.3–1mg/kg; administered via intraperitoneal injection 30 minutes prior to CCL1) dose-dependently inhibited CCL1 (10µg/kg)-induced systemic thermal analgesia[7].
References:
[1] Berenguer J, Lagerweij T, Zhao XW, et al. Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8. J Extracell Vesicles. 2018 Mar 13;7(1):1446660.
[2] García-Domínguez M, González-Rodríguez S, Hidalgo A, et al. Kappa-opioid receptor-mediated thermal analgesia evoked by the intrathecal administration of the chemokine CCL1 in mice. Fundam Clin Pharmacol. 2021 Dec;35(6):1109-1118.
[3] Ding H, Xu X, Zhu Y, et al. Inhibition of Alkbh5 Attenuates Lipopolysaccharide-Induced Lung Injury by Promoting Ccl1 m6A and Treg Recruitment. Cell Prolif. 2025 Sep;58(9):e70032.
[4] Geervliet E, Arora S, Donohue D, et al. Design, molecular characterization and therapeutic investigation of a novel CCR8 peptide antagonist that attenuates acute liver injury by inhibiting infiltration and activation of macrophages. Acta Pharm Sin B. 2025 Apr;15(4):2114-2133.
[5] Oshio T, Kawashima R, Kawamura YI, et al. Chemokine receptor CCR8 is required for lipopolysaccharide-triggered cytokine production in mouse peritoneal macrophages. PLoS One. 2014 Apr 8;9(4):e94445.
[6] Lee Y, Lee J, Park M, et al. Inflammatory chemokine (C-C motif) ligand 8 inhibition ameliorates peritoneal fibrosis. FASEB J. 2023 Jan;37(1):e22632.
[7] García-Domínguez M, Aguirre A, Lastra A, et al. The Systemic Administration of the Chemokine CCL1 Evokes Thermal Analgesia in Mice Through the Activation of the Endocannabinoid System. Cell Mol Neurobiol. 2019 Nov;39(8):1115-1124.
R243是一种CCR8受体抑制剂，R243可抑制由CCL1（CCR8的内源性配体）引发的信号通路[1-2]。R243主要被用于免疫与炎症相关疾病的研究中[3]。
在体外，R243（10μM）处理小鼠RAW264.7巨噬细胞和骨髓来源巨噬细胞（BMDMs）24小时，在CCL1（10ng/mL）诱导的Transwell迁移实验中，R243显著抑制CCL1驱动的巨噬细胞趋化迁移，但对人源THP-1单核细胞的迁移抑制作用不显著[4]。R243（0-10μM）处理经LPS（100ng/mL）刺激小鼠腹膜巨噬细胞（PMφ）24小时，R243显著抑制TNF-α、IL-6和IL-10的分泌，并减弱JNK和NF-κB信号通路的磷酸化水平[5]。
在体内，在腹膜纤维化小鼠模型中，R243（1.0mg/kg；每周三次腹腔注射，持续28天）通过功能性抑制CCR8受体，显著减轻氯己定葡萄糖酸盐诱导的腹膜炎症和腹膜纤维化，表现为腹膜厚度减少、胶原沉积下降及巨噬细胞浸润减[6]。在热痛觉测试模型中，R243（0.3–1mg/kg；在CCL1给药前30分钟腹腔注射）可剂量依赖性抑制CCL1（10μg/kg）诱导的全身性热镇痛效应[7]。