"目录号: HY-13749A
Metabolic Enzyme/ProteaseAutophagy-
Sitagliptin(MK 0431)磷酸盐是DPP4抑制剂，对Caco-2细胞提取物的IC50为19 nM。
Dipeptidyl PeptidaseAutophagy
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生物活性
Description
Sitagliptin phosphate is a potent inhibitor ofDPP4withIC50of 19 nM in Caco-2 cell extracts
IC50& Target
IC50: 19 nM (DPP4, in Caco-2 cell extracts)
In Vitro
Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50of 19 nM from Caco-2 cell extracts[1].?Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation[2].?A recent study demonstrates that sitagliptin exerts a novel, direct action in order to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival[3].?
In Vivo
In vivo, the ED50value of sitagliptin phosphate for inhibition of plasma DPP-4 activity is calculated to be 2.3 mg/kg 7 hour postdose and 30 mg/kg 24 hour postdose in freely fed Han-Wistar rats[1].?The streptozotocin-induced type 1 diabetes mouse model exhibits elevated DPP-4 levels in the plasma that can be substantially inhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation of hyperglycemia, potentially through prolongation of islet graft survival[4].?The plasma clearance and volume of distribution of Sitagliptin phosphate are higher in rats (40-48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); and its half-life is shorter in rats,2 hours compared with 4 hours in dogs[5].?
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