Sitagliptin

SKU: orb1310801

Description

Sitagliptin is a selective DPP-4 inhibitor used in type 2 diabetes research. By blocking DPP-4, it increases active incretin levels, enhancing insulin secretion and suppressing glucagon. This mechanism is widely studied in both in vitro enzymatic assays and in vivo models of metabolic disease.

Research Area

Cell Biology, Pharmacology & Drug Discovery, Protein Biochemistry

Key Properties

• CAS Number: 486460-32-6
• MW: 407.31
• Purity: 99.83% (May vary between batches)
• Formula: C₁₆H₁₅F₆N₅O
• SMILES: N[C@@H](CC(=O)N1CCn2c(C1)nnc2C(F)(F)F)Cc1cc(F)c(F)cc1F
• Target: Autophagy,DPP-4
• Solubility: DMSO:170 mg/mL (417.37 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.91 mM);H2O:< 1 mg/mL (insoluble)

Bioactivity

• Target IC50:
  DPP4:18 nM
• In Vivo:
  In vivo studies demonstrate that the ED50 (effective dose for 50% of the population) of sitagliptin phosphate, which inhibits DPP-4 activity in plasma, is estimated to be 2.3 mg/kg seven hours post-administration and 30 mg/kg twenty-four hours post-administration in freely fed Han-Wistar rats. In the streptozotocin-induced type 1 diabetes mouse model, characterized by elevated plasma DPP-4 levels, sitagliptin phosphate supplementation notably reduces these levels, effectively regulating hyperglycemia and potentially enhancing islet graft longevity. Moreover, pharmacokinetic profiles reveal that both plasma clearance and the volume of distribution for sitagliptin phosphate are significantly higher in rats (40-48 mL/min/kg, 7-9 L/kg) compared to dogs (9 mL/min/kg, 3 L/kg), with a half-life of 2 hours in rats versus 4 hours in dogs.
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• In Vitro:
  Sitagliptin phosphate demonstrates a potent inhibitory effect on dipeptidyl peptidase-4 (DPP-4), achieving an IC50 of 19 nM in Caco-2 cell extracts. It also inhibits in vitro migration of isolated splenic CD4 T-cells through cAMP/PKA/Rac1 pathway activation. Furthermore, sitagliptin directly enhances GLP-1 secretion from intestinal L cells via a pathway that is independent of DPP-4, but relies on protein kinase A and MEK-ERK1/2 activation. Additionally, it mitigates the impact of autoimmunity on graft survival.
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• Cell Research:
  CD4T-cells are plated on membrane inserts in serum-free RPMI 1640, and cell migration is assayed using Transwell chambers (Corning), in the presence or absence of purified porcine kidney DPP-4 (32.1 units/mg; 100 mU/mL final concentration) and DPP-4 inhibitor (100 μM). After 1 hour, cells on the upper surface are removed mechanically, and cells that have migrated into the lower compartment are counted. The extent of migration is expressed relative to the control sample.
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Storage & Handling

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

Alternative Names

Dipeptidyl Peptidase, DPP, DPP4, DPP-4, Autophagy, Inhibitor, inhibit, MK 0431, MK0431, MK-0431, Sitagliptin

Compound Identifiers

PubChem CID

4369359