SRI-42127 is a HuR translocation inhibitor. HuR is an RNA regulator that binds to AREs, and HuR translocations promote the production of inflammatory cytokines in glial cells. However, SRI-42127 can destroy mRNA stability and inhibit gene promoter activation. SRI-42127 also inhibits microglial cell activation and attenuates recruitment/chemotaxis of neutrophils and monocytes[1].
SRI-42127 (0.05-1 μM; 24 h) 阻断 LPS (1 μg/mL) 刺激原代小胶质细胞的 HuR 细胞质转位[1]。
SRI-42127 (0.05-1 μM; 24 h) 抑制激活的原代小胶质细胞 (PMG) 中炎症细胞因子和趋化因子 mRNA 水平[1]。
SRI-42127 (0.5 μM 和 1 μM; 24 h) 阻断胶质细胞产生的中性粒细胞和单核细胞的化学吸引/迁移信号[1]。
SRI-42127 (15 mg/kg; 腹腔注射; 单剂量) 抑制小鼠模型中 HuR 易位和小胶质细胞活化[1]。
[1]. Chellappan R, et al. SRI-42127, a novel small molecule inhibitor of the RNA regulator HuR, potently attenuates glial activation in a model of lipopolysaccharide-induced neuroinflammation. Glia. 2022 Jan;70(1):155-172.