Saxagliptin

SKU: orb1225201

Description

A highly potent, long-acting, orally active DPP4 inhibitor with Ki of 0.6 nM; shows no CYP3A4 inhibition up to 100 uM, and good oral exposure.Diabetes Approved(In Vitro):Saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) treatment significantly induceS β-cell proliferation.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.Saxagliptin acts by preventing the degradation of glucagon-like peptide-1 and hence increases secretion of insulin and decreases secretion of glucagon.(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.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.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 361442-04-8
• MW: 315.41
• Purity: >98% (HPLC)
• Formula: C₁₈H₂₅N₃O₂
• SMILES: C1C2CC2N(C1C#N)C(=O)C(C34CC5CC(C3)CC(C5)(C4)O)N
• Target: DPP
• Solubility: DMSO: ≥ 34 mg/mL

Bioactivity

• 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. 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.
• In Vitro:
  Saxagliptin (100 nM; 48 hours; INS-1 832/13 cells) treatment significantly induceS β-cell proliferation. 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. Saxagliptin acts by preventing the degradation of glucagon-like peptide-1 and hence increases secretion of insulin and decreases secretion of glucagon. Cell Viability Assay Cell line: INS-1 832/13 cells. Concentration: 100 nM. Incubation time: 48 hours. Result: Significantly induced β-cell proliferation. Western blot analysis. Cell line: INS-1 832/13 cells. Concentration: 100 nM. Incubation time: 48 hours. Result: Increased the p-AKT and active β-catenin protein levels, paralleled with the increase of c-myc and cyclin D1 protein expression.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BMS-477118 | BMS 477118 | BMS477118

Quick Database Links

Gene Symbol

DPP