Pirfenidone

一种口服生物可利用的吡啶酮衍生物，具有抗纤维化、抗炎和抗氧化活性；以浓度依赖性方式抑制A549肺癌细胞中TGF-β1刺激的I型胶原蛋白、纤连蛋白和Hsp47表达的增加；在由博来霉素诱发的小鼠肺纤维化模型中，300mg/kg剂量可抑制肺纤维化并抑制胶原含量、纤维细胞池大小以及趋化因子CCL2和CCL12水平的增加；在NASH小鼠模型中，280mg/kg剂量可抑制纤维化并增加肝细胞凋亡、小叶炎症和肝脏纤维化相关基因Col1a1、Timp1、Tgfb1、Pdgfb和Fgf2的表达；抑制绵羊肝微粒体中NADPH依赖的脂质过氧化并清除羟基自由基（IC50分别为~6和~2.5mM）。An orally bioavailable pyridone derivative with antifibrotic, anti-inflammatory, and antioxidant activities; inhibits TGF-β1-stimulated increases in collagen type I, fibronectin, and Hsp47 expression in A549 lung cancer cells in a concentration-dependent manner; inhibits fibrosis and inhibits increases in collagen content, fibrocyte pool size, and the levels of chemokines CCL2 and CCL12 at 300 mg/kg in lung in a mouse model of pulmonary fibrosis induced by bleomycin; inhibits fibrosis and increases in hepatocyte apoptosis, lobular inflammation, and hepatic expression of the fibrosis-related genes Col1a1, Timp1, Tgfb1, Pdgfb, and Fgf2 in a mouse model of NASH at 280 mg/kg; inhibits NADPH-dependent lipid peroxidation in sheep liver microsomes and scavenges hydroxyl radicals (IC50s = ~6 and ~2.5 mM, respectively).