Saxagliptin, also known as BMS-477118, is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Saxagliptin was approved in 2008 for the treatment of type 2 diabetes. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. .
Saxagliptin hydrochloride (BMS-477118 hydrochloride) is a potent, selective, reversible, and orally active inhibitor of dipeptidyl peptidase-4 (DPP-4), with a Ki ranging from 0.6 to 1.3 nM[1].[2].[3].
体内研究
In diabetic rats induced by a high-fat diet and streptozotocin, saxagliptin treatment at 1 mg/kg for 12 weeks leads to significant improvements in pancreatic insulin secretion capacity and an increased β-cell to α-cell areas ratio[1].
Saxagliptin also demonstrates dose-dependent inhibition of plasma DPP-4 activity in Han-Wistar rats, achieving about 70% inhibition with 1 mg/kg and approximately 90% with 10 mg/kg at 7 hours post-dose. At 24 hours post-dose, approximately 20% and 70% inhibition levels are observed, respectively[2].
体外研究
Saxagliptin hydrochloride has the potential for type 2 diabetes mellitus research. In vitro, treatment with Saxagliptin 100 nM for 48 hours, Saxagliptin significantly induces β-cell proliferation. This proliferation is accompanied by increases in phosphorylated AKT and active β-catenin protein levels, along with elevated expression of c-myc and cyclin D1 proteins[1].
Saxagliptin's mechanism involves the inhibition of DPP-4 activity, which prevents the degradation of glucagon-like peptide-1, thus promoting insulin secretion while decreasing glucagon secretion[3].
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