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
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Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors.
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.
期刊介绍：
Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
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