Development of Idiopathic Pulmonary Fibrosis and its Pathogenic Inhibition by Drugs: An Overview

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and incurable inflammatory and fibrotic interstitial lung disease (ILD) of unknown etiology having a high rate of morbidity and mortality throughout the world. The pathophysiology indicates the persistent or repetitive injury of lung epithelial cells through the involvement of genetic and / or environmental factors predominantly in the older population, and the subsequent activation of fibroblasts to differentiate into myofibroblasts followed by the deposition of extracellular matrix (ECM) components such as collagen and the expressions of other genes and proteins and aberrant lung repair through the various signalings leading to scarred and stiff tissue (e.g. parenchymal lung alveoli, interstitium, and capillary endothelium) -formation and irreversible loss of lung function making breathing trouble in transferring oxygen and carbon dioxide between the alveolar space and the blood stream. A few drugs either FDA approved or under clinical trials are being applied to slow / arrest disease progression and relieve symptoms partially, mainly through the inhibition of receptor / non-receptor tyrosine kinases, phosphodiesterase 4B, a pro-apoptotic corisin peptide, and a pro-fibrotic
-galactoside-binding lectin galectin 3 (Gal-3) as anti-fibrotic and anti-inflammatory agents. In recent decades, the emergence of anti-fibrotic therapies has improved the survival of the patients via a cure to some extent. However, it is required further investigations on the mechanistic disease developments and their inhibitions by new drugs with the reflections of clinical phenotypes. This review elucidates the recent data on approved therapies, the key pathogenic information to develop new anti-fibrotic agents, and new compounds in clinical development. Moreover, future directions / strategies for developing efficient vectorized anti-fibrotic agents for specific targeting with the least side effects are depicted.