galectin-6 Inhibitors

Chemical inhibitors of galectin-6 include a variety of compounds that interfere with its ability to interact with glycoprotein targets. TD139, for instance, is known to bind to the carbohydrate recognition domain of galectin-3, and due to structural similarities, it can inhibit galectin-6 by preventing it from engaging with its glycoprotein ligands. Similarly, LacNAc (N-acetyllactosamine), a disaccharide, can serve as a competitive inhibitor to galectin-6 by mimicking the oligosaccharides that the protein naturally binds, thereby obstructing its binding sites. Thiodigalactoside operates on the same principle, resembling the galactoside sugars that galectin-6 typically adheres to, which leads to the blockade of its carbohydrate recognition domain. Furthermore, Davanat, a modified polysaccharide, can inhibit galectin-6 by binding to its recognition domain, thus preventing its interaction with natural ligands.

Other inhibitors affect the protein glycosylation process, which is crucial for the functional interaction of galectin-6 with its glycoprotein targets. Phenylbutylamine can disrupt glycosylation processes, thereby reducing the availability of glycosylated proteins for galectin-6 binding. Castanospermine and Deoxynojirimycin are glucosidase inhibitors that indirectly inhibit galectin-6 by altering the glycosylation of proteins, leading to reduced binding efficiency. Deoxymannojirimycin and Swainsonine inhibit mannosidase enzymes, which are also involved in the glycosylation pathway; their inhibition results in misglycosylated proteins that galectin-6 cannot recognize effectively. Miglustat works by inhibiting glucosylceramide synthase, leading to changes in the synthesis of glycosphingolipids and consequently disrupting the glycosylation patterns recognized by galectin-6. Finally, Cytisine, although not a primary inhibitor of galectins, can bind to the carbohydrate recognition domains of galectin-6. Cytisine can occupy these sites, thus preventing it from interacting with its natural ligands, resulting in functional inhibition.