EL289

EL289 is a potent, selective small-molecule inverse agonist of retinoic acid receptor-related orphan receptor alpha (RORα), a nuclear receptor and circadian regulator. Developed through a collaborative academic effort involving the Biomedical Sciences Research Center 'Alexander Fleming', LMU Munich, Goethe University Frankfurt, and other partners, EL289 exhibits an EC50 of less than 150 nM and demonstrates 20-fold selectivity over RORγ and RORβ. In preclinical models of idiopathic pulmonary fibrosis (IPF), EL289 has demonstrated robust antifibrotic activity, including the reduction of α-SMA, collagen I/III, and fibronectin in TGF-β-stimulated lung fibroblasts, and improvement of tissue architecture in bleomycin-treated precision-cut lung slices. It also suppresses pro-fibrotic markers in macrophages and attenuates fibroblast activation in patient-derived cells, highlighting its potential as a novel therapeutic candidate for IPF.