Galectin 3 (Gal-3) is one of a group of 14 lectins that bind β-galactoside-containing carbohydrates, via
a carbohydrate recognition domain (CRD), and it binds to galectin-3 binding protein
. It plays regulatory functions in multiple biological processes, including cell-cell adhesion, cell-matrix interactions, macrophage activation, leukocyte migration, inflammation, angiogenesis, metastasis, apoptosis [6
] and fibrosis. Galectin 3 is being investigated as a molecular target for the development of novel therapeutics for cancer [9-10
], cardiovascular disease [3
] and fibrosis (e.g
. liver fibrosis in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) [11
]. GM-MD-02 (Galectin Therapeutics) is a galactoarabino-rhamnogalacturonan polysaccharide polymer (pectin) that binds to Gal-3 (Kd
8 μM: Gal-1 Kd
10 μM)) and reduces inflammation and fibrosis-associated effects in experimental models [2
], but no clinical efficacy was observed in Phase 2 evaluation in patients with NASH cirrhosis (NCT02462967), although in the subset of patients with cirrhosis who had no esophageal varices some clinical benefit has been indicated, and Phase 3 testing in this subset of cirrhosis patients is planned.
In relation to cardiovascular disease, galectin 3/galectin 3 binding protein complexes co-localize to the leukocyte/endothelial cell interface of vein walls in mice and galectin 3 increases vein wall IL-6 levels and promotes venous thrombosis [5
]. In human patients, elevated circulating galectin-3 binding protein correlates with acute venous thrombosis.