Saracatinib inhibits TGF-β–induced phenotypic changes in human lung fibroblasts

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications.We investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in in vitro modele using normal human lung fibroblasts (NHLFs). To investigate the effects of saracatinib in pulmonary fibrosis we used a disease-relevant in vitro model. We generated transcriptomic drug signatures by performing bulk RNA sequencing (RNAseq) on Normal Human Lung Fibroblast (NHLF) cells treated with saracatinib, nintedanib, pirfenidone, or vehicle control in the presence or absence of TGF-β stimulation.