Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and rare disease with significant physical and economic impact, affecting between 13 and 20 people per 100,000 and generating healthcare costs of up to ?2 billion annually. With survival of only 3-5 years post-diagnosis, there are currently only two approved drugs (pirfenidone and nintedanib), both are not curative and with limitations. This highlights the urgent need for new antifibrotic molecules, and repurposing FDA-approved drugs could accelerate the development of effective therapies.

Materials and Methods: We have developed an automated high-content screening assay in a 384-well format to measure transforming growth factor-? (TGF?)-induced extracellular matrix (ECM) deposition in lung adenocarcinoma cell line. This assay integrates longitudinal cell imaging with multiparametric analysis to assess extracellular matrix (ECM) deposition. Using this assay we have started the screening of more than 3,500 drugs approved by the FDA and listed in official pharmacopeias. Our objective is to identify drugs with antifibrotic activity.

Results: In the initial optimization phase, we have identified TH10785, a small molecule that activates the DNA glycosylase OGG1, to reduce the expression of ECM markers to baseline levels following TGF-? induction, demonstrating greater antifibrotic efficacy than the approved IPF treatments in this assay.

Conclusion: We have established a cellular high-content screening assay aimed at repurposing FDA-approved and pharmacopeial drugs. An antifibrotic candidate has been identified during the optimization phase, demonstrating the assay?s potential and feasibility.