Molecular Pathways in Idiopathic Pulmonary Fibrosis: A Review of Novel Insights for Drug Design

Abstract

Idiopathic pulmonary fibrosis is a progressive, irreversible lung disease of unknown cause, characterized by gradual thickening and scarring of lung tissue, impairing oxygen transfer into the bloodstream. As a result, symptoms such as shortness of breath, fatigue, and a persistent dry cough occur. Currently, the FDA-approved antifibrotic agents Pirfenidone and Nintedanib can slow the progression of the disease. However, these treatments cannot completely stop the loss of lung function and do not provide a significant improvement in the quality of life of patients. As fibrosis progresses, lung capacity decreases, shortness of breath increases, and general health deteriorates significantly. Therefore, new more effective, and targeted therapies that can halt the progression of IPF are urgently needed. This review addresses novel strategies to slow or halt the disease-related loss of lung function by targeting key mechanisms involved in the pathogenesis of IPF. The molecular structure–activity relationships (SARs) of synthesized compounds targeting JAK/STAT, TGF-β/Smad, Wnt/β-catenin, PI3K, JNK1, and other critical signaling pathways were examined. These targeted approaches have great potential for the development of more potent and selective therapeutic agents for the treatment of IPF. The insights provided in this review may contribute to the future development of more efficient and selective antifibrotic drugs.