Discovery of Galactopyranose‐1‐carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin‐3 Inhibitors

• DOI: 10.1002/cmdc.202401012
• Publication Date: 2025-03-12T10:35:12Z
• Authors: Cornelia Zumbrunn; Luboš Remen; Christoph P. Sager; Corinna Grisostomi; Christina Stamm; Daniela Krüsi; Sven Glutz; Gunther Schmidt; Oliver Nayler; Marc Iglarz; Aengus Mac Sweeney; Alain Chambovey; Manon Müller; Celia Mueller; Geoffroy Bourquin; Solange Meyer; Eva Hühn; Christophe Cattaneo; Magali Vercauteren; John Gatfield; Martin H. Bolli
• Keywords: Galectin; Docking (animal); Galectin-1

Galectin‐3 (Gal‐3), a β‐galactoside‐binding lectin, is implicated in diverse cellular functions ranging from immune response modulation to tissue homeostasis. Notably, increased Gal‐3 expression has been linked the progression of numerous diseases, including cancer, fibrosis, and cardiovascular disorders, underscoring its potential as therapeutic target. Small molecule inhibitors have discovered are valuable tools study such diseases. We report here discovery novel, galactose‐based, small compound 12 which orally bioavailable show efficacy mouse model acute liver injury fibrosis (CCl4 model). The use structure‐based drug design (docking virtual library amides based on acid 2) was key process towards potent, nanomolar inhibitors.