galectin-5 Inhibitors

Galectin-5 inhibitors represent a group of compounds that primarily target the galectin-5 protein, a member of the galectin family known for binding β-galactosides. Galectins, in general, are characterized by their affinity for galactose-containing glycoconjugates, and their interactions play a vital role in numerous cellular processes, including cell adhesion, migration, and signaling. The structure of galectin-5, like other members of its family, includes the carbohydrate recognition domain (CRD), which is the primary site of interaction with galactose moieties. The inhibitors of galectin-5 are thus often designed or identified based on their ability to bind this CRD, effectively disrupting the protein's natural interactions.

The chemical diversity of galectin-5 inhibitors is notable. Many come from or are inspired by saccharides, given the natural carbohydrate-binding behavior of galectins. For example, lactose and N-Acetyllactosamine (LacNAc) are sugars that can bind directly to the CRD of galectins, preventing them from binding to their typical cellular targets. Another approach in designing inhibitors has been to use compounds that mimic these sugars but might offer enhanced binding affinity or specificity. Thiodigalactoside and TDG are examples of such mimetics. Beyond saccharide-based molecules, other classes of compounds, such as aromatic compounds and benzoboroxoles, have also shown potential in inhibiting galectin-5. These compounds, while structurally diverse, usually have moieties that can fit and interact with the CRD of galectin-5. In addition to direct binders, some compounds, like swainsonine, can indirectly affect galectin-5 activity by modifying the availability or structure of its natural ligands.