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Wild-type FGF-21-Fc is a recombinant fusion protein consisting of the native human fibroblast growth factor 21 (FGF21) sequence linked to the Fc (fragment crystallizable) domain of a human immunoglobulin, typically IgG1 or IgG4. FGF21 is an endocrine hormone that regulates energy metabolism, glucose homeostasis, and lipid oxidation by acting as an agonist at the fibroblast growth factor receptor (FGFR) complex, specifically requiring the co-receptor beta-Klotho for high-affinity binding and signaling. The fusion to an Fc domain is a protein engineering strategy employed to overcome the extremely short half-life of native FGF21 (approximately 0.5 to 2 hours) by increasing the molecule's hydrodynamic radius and enabling neonatal Fc receptor (FcRn)-mediated recycling. In the development of metabolic therapies, wild-type FGF-21-Fc is frequently used as a benchmark or control to evaluate the enhanced potency, stability, or synergistic effects of second-generation FGF21 analogs, mutated variants, or multi-agonist fusion proteins (such as FGF21/GLP-1 dual agonists) intended for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH).
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