Epigenetic targets and their inhibitors in the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease characterized by fibroblast proliferation, excessive extracellular matrix buildup, inflammation, and tissue damage, resulting in respiratory failure and death. Recent studies suggest that impaired interactions among epithelial, mesenchymal, immune, and endothelial cells play a key role in IPF development. Advances in bioinformatics have also linked epigenetics, which bridges gene expression and environmental factors, to IPF. Despite the incomplete understanding of the pathogenic mechanisms underlying IPF, recent preclinical studies have identified several novel epigenetic therapeutic targets, including DNMT, EZH2, G9a/GLP, PRMT1/7, KDM6B, HDAC, CBP/p300, BRD4, METTL3, FTO, and ALKBH5, along with potential small-molecule inhibitors relevant for its treatment. This review explores the pathogenesis of IPF, emphasizing epigenetic therapeutic targets and potential small molecule drugs. It also analyzes the structure-activity relationships of these epigenetic drugs and summarizes their biological activities. The objective is to advance the development of innovative epigenetic therapies for IPF.