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, Eva Hühn, Christophe Cattaneo, Magali Vercauteren, John Gatfield, Martin H Bolli, Solange Meyer, Geoffroy Bourquin
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引用次数: 0
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.
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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.
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