FGF21-164

FGF21-164 is a novel recombinant human fibroblast growth factor 21 (FGF21) analog engineered by fusing a mutated FGF21 gene with a tandem repeat (TR) region of human CD164 (hCD164/MUC24) using fusion protein technology. The modifications—including N-terminal truncation (ΔHPIP) and point mutations (L118C, A134C)—are designed to enhance the molecule's stability, solubility, and serum half-life through heavy glycosylation and sialylation provided by the hCD164 TR fusion partner. FGF21-164 functions as an agonist at the FGF21 receptor (FGFR1c/β-Klotho complex), activating downstream signaling pathways (e.g., Erk1/2 phosphorylation) to regulate glucose and lipid metabolism. In preclinical mouse models (ob/ob and diet-induced obese mice), FGF21-164 demonstrated pronounced glucose-lowering effects, reduced hepatic fat accumulation, and prolonged pharmacological efficacy following single subcutaneous injection, with sustained effects seen for up to 28 days. The drug is under preclinical development for metabolic diseases, particularly obesity, diabetes, and nonalcoholic steatohepatitis (NASH)[1].