Sitagliptin

Sitagliptin (MK-0431) is an orally active and highly selective DPP4 inhibitor with an IC50 value of 19 nM. Sitagliptin blocks the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) by competing inhibition mechanism (Kᵢ = 1 nM), thereby increasing the level of active incretin. Sitagliptin can also directly stimulate the secretion of GLP-1 by intestinal L cells by activating the cAMP/PKA and ERK1/2 pathways, and this effect is independent of DPP-4. Sitagliptin shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin can be used for the study of 1-type and 2-type diabetes[1][2][3][4][5].

Product Specifications

CAS Number

[486460-32-6]

Product Name Alternative

MK-0431

UNSPSC

12352005

Hazard Statement

H319, H373

Target

Dipeptidyl Peptidase; Endogenous Metabolite; ERK; GLP Receptor; PKA

Type

Reference compound

Related Pathways

GPCR/G Protein; MAPK/ERK Pathway; Metabolic Enzyme/Protease; Stem Cell/Wnt; TGF-beta/Smad

Applications

Metabolism-protein/nucleotide metabolism

Field of Research

Metabolic Disease

Assay Protocol

https://www.medchemexpress.com/Sitagliptin.html

Purity

99.94

Solubility

DMSO : ≥ 100 mg/mL

Smiles

O=C(N1CC2=NN=C(C(F)(F)F)N2CC1)C[C@H](N)CC3=CC(F)=C(F)C=C3F

Molecular Formula

C16H15F6N5O

Molecular Weight

407.31

Precautions

H319, H373

References & Citations

[1]Thomas, L., et al. (R) -8- (3-amino-piperidin-1-yl) -7-but-2-ynyl-3-methyl-1- (4-methyl-quinazolin-2-ylmethyl) -3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther. 2008 Apr;325 (1) :175-82.|[2]Kim, S.J., et al., Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes, 2009. 58 (3) : p. 641-51.|[3]Sangle, G.V., et al., Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a GLP-1 secretagogue. Endocrinology, 2012. 153 (2) : p. 564-73.|[4]Kim, S.J., et al., Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes, 2008. 57 (5) : p. 1331-9.|[5]Beconi, M.G., et al. Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs. Drug Metab Dispos, 2007. 35 (4) : p. 525-32.