2-Acetamidophenol

2-Acetamidophenol (Orthocetamol) is a regulator that targets ferroptosis and glutathione metabolic pathways, is the ortho-regioisomer of Paracetamol (HY-66005). 2-Acetamidophenol has anti-atherosclerotic activity, and inhibiting total cholesterol (TC) and triglyceride (TG) in a zebrafish hyperlipidemia model with IC₅₀s for 30 μM and 40 μM, respectively. 2-Acetamidophenol upregulates the expression of glutathione synthesis-related genes (such as GCLC, GCLM, GSS) and iron ion transport genes (such as FPN1, FTH), reduces the accumulation of intracellular reactive oxygen species (ROS) and ferrous ions (Fe²⁺), and enhances the activity of glutathione peroxidase GPX4, thereby inhibiting macrophage phagocytosis of oxidized low-density lipoprotein (ox-LDL) and foam cell formation^[1][2]. In Vitro:In zebrafish hyperlipidemia model experiments, 2-Acetamidophenol (20-80 μM; 48 h) significantly improves lipid metabolism, reducing total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) levels, increasing high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (T-SOD) activity, reducing intravascular macrophage aggregation, and enhancing blood flow velocity^[1]. In RAW264.7 macrophage foam cell model experiments, 2-Acetamidophenol (10-40 μM; 24 h) inhibits oxidized low-density lipoprotein (ox-LDL)-induced lipid phagocytosis, reduces intracellular TC, TG, free cholesterol (FC), cholesterol ester (CE) contents, and the CE/TC ratio, decreases reactive oxygen species (ROS) and ferrous ion Fe²⁺ accumulation, and enhances glutathione peroxidase 4 (GPX4) activity^[1]. In Vivo:2-Acetamidophenol (20-80 μM; immersion administration; daily medium replacement; 48 h) in zebrafish (AB strain, 5 days post-fertilization) hyperlipidemia models significantly improves lipid metabolism, reduces total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) levels, increases high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (T-SOD) activity, decreases intravascular macrophage aggregation, and accelerates blood flow velocity^[1].