Galectin-3 is a carbohydrate-binding protein whose expression has been shown to play a central role in fibrosis and cancer. Galectin-3 has been linked to a number of biologic processes including inflammation, aberrant cell activation and proliferation (involving macrophages, neutrophils, and mast cells), fibrogenesis and ultimately, organ dysfunction. Experimental data have implicated Galectin-3 in a variety of diseases across a number of organ systems, including liver, kidney, lung, and heart. Notably, blockade of Galectin-3 has been shown to prevent and even reverse fibrosis following organ damage, making it a promising therapeutic strategy.
Current research also indicates that galectins have important roles in modulating the immune and inflammatory response to cancer that contributes to neoplastic transformation, tumor cell survival, angiogenesis and metastasis.
Applying our understanding of carbohydrate biology and chemistry, we have rationally designed several highly potent, selective, oral small-molecule “glycomimetic” antagonists of Galectin-3. These novel compounds have proven anti-fibrotic and antitumor activity, as demonstrated in various animal models of disease. In March of 2022, GMI-2093 was selected as the lead Galectin-3 antagonist for further pre-clinical development.
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