1. Academic Validation
  2. Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors

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

  • ChemMedChem. 2025 Mar 12:e202401012. doi: 10.1002/cmdc.202401012.
Cornelia Zumbrunn 1 Luboš Remen 1 Christoph P Sager 1 Corinna Grisostomi 1 Christina Stamm 1 Daniela Krüsi 1 Sven Glutz 1 Gunther Schmidt 1 Oliver Nayler 1 Marc Iglarz 1 Aengus Mac Sweeney 1 Alain Chambovey 1 Manon Müller 1 Celia Mueller 1 Geoffroy Bourquin 1 Solange Meyer 1 Eva Hühn 1 Christophe Cattaneo 1 Magali Vercauteren 1 John Gatfield 1 Martin H Bolli 1
Affiliations

Affiliation

  • 1 Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123, Allschwil, Switzerland.
Abstract

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 to the progression of numerous diseases, including Cancer, fibrosis, and cardiovascular disorders, underscoring its potential as a therapeutic target. Small molecule inhibitors have been discovered and are valuable tools to study such diseases. We report here the discovery of novel, galactose-based, small molecule inhibitors such as compound 12 which are orally bioavailable and show efficacy in a mouse model of acute liver injury and fibrosis (CCl4 model). The use of structure-based drug design (docking of a virtual library of amides based on acid 2) was key in the process towards potent, nanomolar inhibitors.

Keywords

Galectin-3; cancer; fibrosis; inflammation; inhibitor.

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