HSF1/AMPK activator 1

HSF1/AMPK activator 1 is a compound that modulates the HSF1/AMPK axis and the TGF-β1/Smad signaling pathway. It exhibits anti-hepatic fibrosis activity and metabolic stability. This activator inhibits fibrosis formation and cell proliferation in activated hepatic stellate cells and improves liver damage and fibrosis symptoms in fibrotic mice. HSF1/AMPK activator 1 is applicable in studies related to liver fibrosis.

HSF1/AMPK activator 1 (Compound 11) effectively inhibits fibronectin expression in TGF-β1-treated human LX-2 cells with an IC50 of 0.7 μM, achieving a 91.6 ± 3.8% inhibition rate at 10 μM over 48 hours without cytotoxicity. At concentrations up to 80 μM over 48 hours, it exhibits no cytotoxicity in human LX-2 and HEK-293 cells. This compound also suppresses the proliferation of TGF-β1-treated human LX-2 cells in a dose-dependent manner. Furthermore, it reduces the expression of fibrosis markers such as fibronectin, type I collagen, and α-smooth muscle actin (α-SMA) at both transcriptional and translational levels. In human LX-2 cells, it inhibits TGF-β1-induced Smad3 phosphorylation and nuclear translocation, thereby suppressing the TGF-β1/Smad signaling pathway. Additionally, in TGF-β1-treated murine hepatic stellate cells, it reduces proliferation, fibrosis, and the TGF-β1/Smad signaling pathway in a dose-dependent manner. HSF1/AMPK activator 1 dose-dependently activates the HSF1/AMPK metabolic pathway in both TGF-β1-treated human LX-2 cells and murine hepatic stellate cells, enhancing the phosphorylation of AMPK and HSF1 and promoting nuclear localization of activated HSF1.

HSF1/AMPK activator 1 (compound 11) administered at a dose of 10-30 mg/kg via intraperitoneal injection every other day for 4 weeks can significantly improve liver damage, inflammation, and fibrosis in mice treated with CCl4.