Sitagliptin phosphate is a potent inhibitor of DPP-IV with IC50 of 19 nM in Caco-2 cell extracts.
Targets:DPP-4
IC50:19 nM
In vitro:As an orally active agent, Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50 of 19 nM from Caco-2 cell extracts.  MK0431 reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation. 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.
In vivo:In vivo, the ED50 value 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. 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.  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.
Features:A potent, orally active inhibitor of DPP-4.

Trelagliptin
E-64
AEBSF HCl
Glimepiride
Saxagliptin
Linagliptin
Vildagliptin
Alogliptin
MG-132
Bortezomib