4-methylquinazoline and Idiopathic-Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease, and its molecular pathogenesis remains poorly understood. Recently, emerging evidence demonstrates that the PI3K signaling transduction pathway is linked to the pathology of IPF. In this work, we rationally designed a new series of 4-methylquinazoline derivatives as highly potent PI3K inhibitors that significantly suppress the phosphorylation of the main PI3K downstream effectors and displays marked antiproliferative activity in mouse MLg2908 lung fibroblasts. In a bleomycin-induced mouse pulmonary fibrosis model,

Topics: Animals; Bleomycin; Cell Line; Cell Proliferation; Crystallography, X-Ray; Drug Evaluation, Preclinical; Half-Life; Humans; Idiopathic Pulmonary Fibrosis; Isoenzymes; Lung; Mice; Mice, Inbred ICR; Molecular Conformation; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Quinazolines; Signal Transduction; Structure-Activity Relationship