Galectin-3 (Gal-3) (Gal-3)

Galectin-3 is a 30-35 kDa protein belonging to the lectin family and is the only chimera-type galectin found in mammals [1.2.4, 1.5.1]. It is characterized by a C-terminal carbohydrate recognition domain (CRD) that binds beta-galactoside sugars and an N-terminal domain that allows for multimerization into pentamers [1.3.1, 1.4.1]. Galectin-3 is ubiquitously expressed and localized in the nucleus, cytoplasm, and extracellular space, where it regulates critical biological processes such as cell adhesion, apoptosis, and inflammatory signaling [1.2.5, 1.5.2]. Pathologically, it is a central mediator of chronic inflammation and organ fibrosis in the heart, liver, and lungs, and it significantly contributes to cancer progression by promoting angiogenesis and immune evasion [1.1.1, 1.3.2]. Due to its involvement in these diverse diseases, the CRD has become a high-priority therapeutic target [1.3.3, 1.4.2]. Current drug development efforts focus on small-molecule and carbohydrate-based inhibitors, such as belapectin and GB1211, which are being evaluated in clinical trials for treating metabolic dysfunction-associated steatohepatitis (MASH) and various fibrotic conditions [1.3.5, 1.4.2].

Other names

LGALS3MAC-2 antigenCarbohydrate-binding protein 35 (CBP-35)Lectin L-29L-31L-34IgE-binding proteinAdvanced glycation end-product receptor 335 kDa lectinGalactoside-binding protein (GALBP)

Galectin-3 inhibitors primarily target the carbohydrate recognition domain (CRD) to competitively block the binding of beta-galactoside-containing ligands. This inhibition prevents the formation of galectin-lattices on the cell surface, which otherwise cluster receptors and initiate signaling pathways leading to inflammation, myofibroblast activation, and tumor cell survival [1.3.2, 1.3.3, 1.4.1].