DPP4 belongs to the dipeptidyl peptidases family. DPP4 is a serine protease detected on several immune cells and on epithelial cells of various organs. Besides the membrane-bound enzyme, a catalytically active soluble form is present in several body fluids. Moreover, DPP4 plays a key role in immune-regulation, inflammation, oxidative stress, cell adhesion, and apoptosis by targeting different substrates. Therefore, DPP4 inhibitors are commonly potential hypoglycemic agents.As reported, Saxagliptin (BMS-477118) is a potent, selective, reversible, competitive and orally active DPP-4 inhibitor (Ki = 0.6-1.3 nM). Meanwhile, Saxagliptin inhibits plasma DPP-4 activity and increases insulin secretion in animal models. Thus, Saxagliptin can be used for type 2 diabetes mellitus research. Sitagliptin has been approved by FDA.

Saxagliptin, a DPP4 Inhibitor, is a hypoglycemic agent for diabetes research.

In vitro, in detailed cellular studies conducted on INS-1 832/13 cells, Saxagliptin (100 nM; 48 hours) significantly induces β-cell proliferation. Concurrently, it increases the protein levels of p-AKT and active β-catenin. This upregulation is accompanied by an increase in the expression of c-myc and cyclin D1 proteins, crucial mediators of cell cycle progression. Therefore, through these interconnected pathways, Saxagliptin exerts a profound impact on cellular function and metabolism, underscoring its potential as a valuable tool in managing metabolic diseases.

In a model of high-fat diet/streptozotocin-induced diabetic rats, Saxagliptin (1 mg/kg for 12 weeks) notably improves pancreatic insulin secretion and increased the β-cell to α-cell ratio. Moreover, Saxagliptin dose-dependently inhibits plasma DPP-4 activity in Han-Wistar rats, with ~70% and ~90% inhibition at 7 hours post-dose for 1 mg/kg and 10 mg/kg respectively, and substantial inhibitory effects remaining at 24 hours post-dose.

In conclusion, Saxagliptin is an orally active DPP4 inhibitor. Furthermore, Saxagliptin shows potent hypoglycemic effect in diabetic animal models.


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