Saxagliptin

Saxagliptin (BMS-477118) is a potent, selective, reversible, competitive and orally active dipeptidyl peptidase-4 (DPP-4) (K_i = 0.6-1.3 nM) inhibitor. Saxagliptin has the peotential for type 2 diabetes mellitus research^[1][2][3]. IC50 & Target: Ki: 0.6-1.3 nM (Dipeptidyl peptidase-4 (DPP-4))^[2] In Vitro: Saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) treatment significantly induceS β-cell proliferation^[1].
Saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) treatment increases the p-AKT and active β-catenin protein levels, paralleled with the increase of c-myc and cyclin D1 protein expression^[1].
Saxagliptin acts by preventing the degradation of glucagon-like peptide-1 and hence increases secretion of insulin and decreases secretion of glucagon^[3]. In Vivo: Saxagliptin (1 mg/kg; for 12 weeks) treatment in high-fat diet/streptozotocin-induced diabetic rats, significant improvement in pancreas insulin secretion capacity evaluated by hyperglycemia clamp and increased β-cell to α-cell areas ratio are observed^[1].
Saxagliptin dose-dependently inhibits plasma DPP-4 activity in Han-Wistar rats, by ~70% at 7 hours postdose with 1 mg/kg and by ~90% at 7 hours postdose with 10 mg/kg. At 24 hours postdose, ~20% and 70% inhibition, respectively, remained^[2].