PsTag-FGF21

PsTag-FGF21 is a **long-acting recombinant protein fusion drug** that joins human fibroblast growth factor 21 (FGF21) with a synthetic, uncharged polypeptide extension called PsTag to dramatically extend its half-life and therapeutic activity. FGF21 is an endogenous hormone with central roles in regulating metabolism, especially glucose and lipid metabolism, and is being explored for treatment of metabolic diseases. Native FGF21 has a very short half-life and is impractical as a therapeutic; fusing it to PsTag extends the half-life in mice from less than 1 hour to over 12 hours, while retaining biological activity[1][5][9][10]. Preclinical studies show that PsTag-FGF21 reduces hepatic steatosis and fibrosis, body weight, blood glucose, and lipid levels in rodent models of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD/MASH)[1][5][9][10]. Mechanistic studies found PsTag-FGF21 reduces liver fibrosis by modulating hepatic stellate cell (HSC) activity (e.g., reducing α-SMA, collagen I, TGF-β), shifting macrophages from a pro-inflammatory to anti-inflammatory phenotype, and regulating key transcription factors (e.g., NR4A1) and matrix metalloproteinases, thus improving multiple features of advanced metabolic liver disease[1][9]. PsTag-FGF21 acts through the FGF21 receptor complex (FGFR1c/2c/3c with β-Klotho), resulting in pleiotropic metabolic, anti-inflammatory, and anti-fibrotic effects. Its improved pharmacokinetics and non-immunogenic properties make it a promising candidate for advanced metabolic disease, especially non-alcoholic fatty liver disease (MASLD/MASH/fibrosis), obesity, and diabetes[1][5][9][10]. As of 2025, PsTag-FGF21 has not advanced to late-phase or human clinical trials; extensive data exist from animal models. The developer has described its potential as an alternative to PEGylated proteins, with possibly fewer side effects[5][9].

Other names

PsTag-FGF21PsTag-FGF-21PsTag-FGF 21