TY - JOUR T1 - GTX-003 reduces the fibrotic markers in human lung fibroblast from patients with interstitial lung diseases. JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2022.295 VL - 60 IS - suppl 66 SP - 295 AU - A Montes Worboys AU - J Mercade AU - M Molina-Molina AU - E Ruiz-Canovas Y1 - 2022/09/04 UR - http://erj.ersjournals.com/content/60/suppl_66/295.abstract N2 - Introduction: Fibrotic interstitial lung diseases (ILDs) comprise a heterogeneous group of ILDs characterized by different degrees of inflammation and fibrosis and associated with substantial morbidity and mortality. GTX-003 is a small molecule developed by GAT Therapeutics for the treatment of fibrotic diseases. It is a first-in-class drug with a novel mechanism of action; a non-steroidal allosteric and pleiotropic modulator of subfamily 3C nuclear receptors (NR3C), acting on mineralocorticoid receptor, androgen receptor, and with high affinity for the glucocorticoid receptor. This compound has been proved to reduce TGF-β1 induced fibrosis in different hepatic cell lines.We aimed to investigate the effect of GTX-003 in human fibrotic fibroblasts.Methods: Human lung fibroblasts from ILD patients (IPF n=7, sarcoidosis n=5, hypersensitivity pneumonitis n=5, and controls from non-fibrotic disease n=4) were isolated and co-cultured with GTX-003 (1μM) and TGF-β1 (5 ng/ml) for 72h. Gene and protein expression of major pro-fibrotic markers were analyzed.Results: GTX-003 inhibited the gene expression of the main components of the extracellular matrix; collagen-III (Col3A1), EDA-Fibronectin (EDA-FN), tenascin-C (TNC-C), and metalloproteinase-1 (MMP-1) after the induction with TGF-β1. Moreover, the TGF-β1-induced increase of pro-inflammatory cytokines IL6 and IL8 was reduced by treatment with GTX-003. Protein expression determined by Western blot or ELISA multiplex assay supported gene expression results.Conclusions: The anti-fibrotic and anti-inflammatory properties of GTX-003 make it a promising therapy for fibrotic ILDs.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 295.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -