Targeting galectin-3 in inflammatory and fibrotic diseases.

Galectin (Gal)-3 is a multifunctional lectin present in biological fluids and tissues with a widespread distribution within the cell, the plasma membrane, and extracellular matrix. Gal-3 binds hundreds of ligands with preferential affinity for those possessing β-galactoside motifs, through its carbohydrate recognition domain. The still poorly understood mode of action of Gal-3 must be regarded with respect to the variety of its binding partners. Gal-3 modulates biological processes depending on its own levels, but also on those of its ligands, each possessing its own function. Increased Gal-3 levels are associated with inflammation and fibrosis, highlighting its value as a biomarker and/or therapeutic target in many related diseases. The identification of selective and potent Gal-3 inhibitors is challenging. Novel generation compounds capable of alleviating pathogenic events emphasize the role of Gal-3 as a direct disease target. Galectin (Gal)-3 is a β-galactoside-binding lectin emerging as a key player in cardiac, hepatic, renal, and pulmonary fibrosis and inflammation, respiratory infections caused by COVID-19, and neuroinflammatory disorders. Here, we review recent information highlighting Gal-3 as a relevant therapeutic target in these specific disease conditions. While a causal link was difficult to establish until now, we discuss how recent strategic breakthroughs allowed us to identify new-generation Gal-3 inhibitors with improved potency, selectivity, and bioavailability, and report their usefulness as valuable tools for proof-of-concept studies in various preclinical models of the aforementioned diseases, with emphasis on those actually in clinical stages. We also address critical views and suggestions intended to expand the therapeutic opportunities provided by this complex target. [ABSTRACT FROM AUTHOR]