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Sitagliptin phosphate (MK431; Januvia), the phosphate salt of Sitagliptin, is an antihyperglycemic agent (sugar-lowering) and antidiabetic medication that act as a potent inhibitor of DPP-IV (dipeptidyl peptidase-4) with IC50 of 19 nM in Caco-2 cell extracts.
ln Vitro |
Sitagliptin phosphate potently inhibits DPP-4 in Caco-2 cell extracts with an IC50 of 19 nM [1]. Sitagliptin inhibits the migration of isolated splenic CD4 T cells in vitro via activating the cAMP/PKA/Rac1 pathway [2]. According to a recent study, sitagliptin stimulates intestinal L cells' production of GLP-1 by a unique direct effect that is dependent on MEK-ERK1/2 and protein kinase A but not DPP-4. As a result, it lessens autoimmunity's negative effects on graft survival [3].
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ln Vivo |
The ED50 of sitagliptin phosphate for suppressing plasma DPP-4 activity was determined to be 2.3 mg/kg 7 hours post-dose and 30 mg/kg 24 hours post-dose in vivo in Han-Wistar rats fed at ad libitum [1]. Elevated levels of plasma DPP-4 are shown in a mouse model of type 1 diabetes caused by streptozotocin; mice given a diet high in sitagliptin phosphate had much lower levels of this protein. This is accomplished by improving the management of hyperglycemia, maybe by extending islet transplant survival [4]. Rats have a greater volume of distribution and plasma clearance of sitagliptin phosphate (40-48 mL/min/kg, 7-9 L/kg) than dogs (9 mL/min/kg, 3 L/kg); the half-life of the drug is lower in rats (2 hours) than in dogs (4 hours) [5].
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References |
[1]. 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
[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 glucagon-like peptide-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 |
Molecular Formula |
C₁₆H₁₈F₆N₅O₅P
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Molecular Weight |
505.31
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CAS # |
654671-78-0
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Related CAS # |
Sitagliptin;486460-32-6;Sitagliptin-d4 phosphate;1432063-88-1;Sitagliptin phosphate monohydrate;654671-77-9;(S)-Sitagliptin phosphate;823817-58-9;(Rac)-Sitagliptin;823817-56-7
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
P(=O)(O[H])(O[H])O[H].FC(C1=NN=C2C([H])([H])N(C(C([H])([H])[C@@]([H])(C([H])([H])C3=C([H])C(=C(C([H])=C3F)F)F)N([H])[H])=O)C([H])([H])C([H])([H])N21)(F)F
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Synonyms |
Januvia MK0431 phosphateMK 0431 phosphateMK-0431 phosphate
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~100 mg/mL (~197.90 mM)
H2O : ~50 mg/mL (~98.95 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (98.95 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.9790 mL | 9.8949 mL | 19.7898 mL | |
5 mM | 0.3958 mL | 1.9790 mL | 3.9580 mL | |
10 mM | 0.1979 mL | 0.9895 mL | 1.9790 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.