CU-CPT8m

一种Toll样受体8（TLR8）拮抗剂（解离常数Kd=220纳摩尔；在报告基因试验中半数抑制浓度IC50=67纳摩尔）；在浓度为1微摩尔时，相较于其他所有人源Toll样受体，对TLR8具有选择性；在过表达TLR8的HEK-Blue细胞中，以1微摩尔的浓度抑制TLR8激动剂R-848诱导的肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）mRNA表达升高；以浓度依赖的方式抑制R-848诱导的分化THP-1单核细胞和人外周血单核细胞（PBMCs）中TNF-α蛋白水平的升高；降低骨关节炎患者滑膜细胞中TNF-α和IL-8的水平，以及类风湿关节炎患者PBMCs中TNF-α的水平。An antagonist of TLR8 (Kd = 220 nM; IC50 = 67 nM in a reporter assay); is selective for TLR8 over a panel of all other human TLRs at 1 μM; inhibits increases in TNF-α and IL-8 mRNA expression induced by the TLR8 agonist R-848 in TLR8-overexpressing HEK-Blue cells at 1 μM; inhibits R-848-induced increases in TNF-α protein levels in differentiated THP-1 monocytes and human PBMCs in a concentration-dependent manner; decreases TNF-α and IL-8 levels in synovial cells derived from patients with osteoarthritis and TNF-α levels in PBMCs derived from patients with rheumatoid arthritis.