Saxagliptin

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种高效、长效、口服活性的 DPP4 抑制剂，Ki 为 0.6 nM。

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.

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.

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.

BMS-477118 | BMS 477118 | BMS477118

Metabolic Enzyme/Protease

DPP

DPP-4

Metabolic Disease

Diabetes

361442-04-8

315.41

C18H25N3O2

>98% (HPLC)

DMSO: ≥ 34 mg/mL

C1C2CC2N(C1C#N)C(=O)C(C34CC5CC(C3)CC(C5)(C4)O)N

2-Azabicyclo[3.1.0]hexane-3-carbonitrile, 2-[(2S)-2-amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-, (1S,3S,5S)-

(-20℃)

With Ice Pack

≥ 2 years