Sitagliptin-d4 (phosphate)

Sitagliptin-d4 phosphate (MK-0431-d4) is the deuterium labeled Sitagliptin phosphate (HY-13749A) . Sitagliptin phosphate is an orally active and highly selective DPP4 inhibitor with an IC50 value of 19 nM. Sitagliptin phosphate 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 phosphate 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 phosphate shows protective effects on pancreatic islet grafts in 1-type diabetes models. Sitagliptin phosphate can be used for the study of 1-type and 2-type diabetes.

Product Specifications

CAS Number

[1432063-88-1]

Product Name Alternative

MK-0431-d4 (phosphate)

UNSPSC

12352005

Target

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

Type

Isotope-Labeled Compounds

Related Pathways

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

Applications

COVID-19-immunoregulation

Field of Research

Metabolic Disease

Purity

99.48

Solubility

DMSO : 83.33 mg/mL (ultrasonic)

Smiles

P(=O)(O)(O)O.C(F)(F)(F)C=1N2C(CN(C(C[C@@H](CC3=C(F)C=C(F)C(F)=C3)N)=O)C(C2([2H])[2H])([2H])[2H])=NN1

Molecular Formula

C16H14D4F6N5O5P

Molecular Weight

509.33

References & Citations

[1]Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53 (2) :211-216.|[2]Thomas, L., et al. (R) -8- (3-amino-piperidin-1-yl) -7-but-2-ynyl-3-methyl-1- (4-methyl-quinazolin-2-ylm ethyl) -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 acti|[3]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.|[4]Sangle, G.V., et al., Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue. Endocrinology, 2012. 153 (2) : p. 564-73.|[5]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.|[6]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.