| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Sitagliptin phosphate (formerly also known as MK-431; trade name Januvia; Xelevia; Janumet) monohydrate, is an oral bioavailable, triazolopyrazine-based, potent inhibitor of DPP-IV (dipeptidyl peptidase-4) with an IC50 of 19 nM in Caco-2 cell extracts. It is an antihyperglycemic and antidiabetic medication.
| Targets |
DPP-4 (IC50 = 19 nM)
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|---|---|
| ln Vitro |
Sitagliptin phosphate shows a strong inhibitory action on DPP-4 from extracts of Caco-2 cells, with an IC50 of 19 nM[1]. Via a mechanism involving cAMP/PKA/Rac1 activation, sitagliptin decreases the in vitro migration of isolated splenic CD4 T-cells[2]. A recent study shows that sitagliptin stimulates intestinal L cell GLP-1 secretion through a novel, direct action that is dependent on MEK-ERK1/2 and protein kinase A, but not on DPP-4. As a result, it lessens the impact of autoimmunity on graft survival[3].
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| ln Vivo |
For sitagliptin phosphate to inhibit plasma DPP-4 activity in vivo, the ED50 value in freely fed Han-Wistar rats is estimated to be 2.3 mg/kg seven hours postdose and 30 mg/kg twenty-four hours postdose[1]. Elevated DPP-4 levels in the plasma are seen in the streptozotocin-induced type 1 diabetes mouse model, but these levels can be significantly reduced in mice fed Sitagliptin phosphate. This is accomplished by possibly prolonging islet graft survival through a beneficial effect on the regulation of hyperglycemia[4]. Sitagliptin phosphate's plasma clearance and volume of distribution are higher in rats (40–48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); additionally, rats' half-lives are shorter—two hours versus four hours in dogs[5].
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| Enzyme Assay |
Confluent Caco-2 cells are used to extract DPP-4. Following a 5-minute room temperature incubation period with lysis buffer (10 mM Tris-HCl, 150 mM NaCl, 0.04 U/mL aprotinin, 0.5% Nonidet P40, pH 8.0), the cells are centrifuged at 35,000 g for 30 minutes at 4 °C, and the supernatant is kept at -80°C afterwards. Twenty microliters of suitable compound dilutions are combined with fifty microliters of H-Ala-Pro-7-amido-4-trifluoromethylcoumarin (final concentration in the assay: 100 microliters) as the substrate for the DPP-4 enzyme, and thirty microliters of the Caco-2 cell extract (diluted 1000 times with 100 mM Tris-HCl, 100 mM NaCl, pH 7.8). Fluorescence is measured using a SpectraMax GeminiXS at excitation/emission wavelengths of 405/535 nm after plates are incubated for one hour at room temperature. After exposing Caco-2 cell extracts to high inhibitor concentrations (30 nM for BI 1356 and 3 μM for vildagliptin) for one hour, the dissociation kinetics of the inhibitors from the DPP-4 enzyme are ascertained. Once the preincubation mixture has been diluted 3000-fold with assay buffer, the enzymatic reaction is initiated by adding the substrate, H-Ala-Pro-7-amido-4-trifluoromethylcoumarini. The amount of an inhibitor that is still bound to the DPP-4 enzyme is indicated by the difference in DPP-4 activity at a given time in the presence or absence of the inhibitor. Using the SoftMax software of the SpectraMax, maximum reaction rates (fluorescence units/seconds × 1000) are calculated at 10-minute intervals and corrected for the rate of an uninhibited reaction [(vcontrol-vinhibitor)/vcontrol].
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| Cell Assay |
Membrane inserts containing CD4T-cells are plated in serum-free RPMI 1640. Cell migration is measured using Corning Transwell chambers, either with or without DPP-4 inhibitor (100 μM) and purified porcine kidney DPP-4 (32.1 units/mg; final concentration of 100 mU/mL). Following an hour, cells that have moved into the lower compartment are counted and those on the upper surface are mechanically removed. The expression for the amount of migration is in relation to the control sample.
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| Animal Protocol |
Mice: C57BL/6J mice that have been fasted overnight are challenged with an oral glucose load (2 g/kg) 45 minutes after the compound is administered. Tail bleed predose and successive time points following the glucose load are used to draw blood samples for glucose measurement. DPP-4 inhibitors or a vehicle are given 16 hours prior to the glucose challenge in order to assess how long the effect lasts on glucose tolerance.
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| References |
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| Molecular Formula |
C16H20F6N5O6P
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|---|---|
| Molecular Weight |
523.32
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| Exact Mass |
523.10553934
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| Elemental Analysis |
C, 36.72; H, 3.85; F, 21.78; N, 13.38; O, 18.34; P, 5.92
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| CAS # |
654671-77-9
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| Related CAS # |
Sitagliptin;486460-32-6;Sitagliptin phosphate;654671-78-0;(S)-Sitagliptin phosphate;823817-58-9;(Rac)-Sitagliptin;823817-56-7
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| Appearance |
Solid powder
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| SMILES |
C1CN2C(=NN=C2C(F)(F)F)CN1C(=O)C[C@@H](CC3=CC(=C(C=C3F)F)F)N.O.OP(=O)(O)O
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| InChi Key |
GQPYTJVDPQTBQC-KLQYNRQASA-N
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| InChi Code |
InChI=1S/C16H15F6N5O.H3O4P.H2O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22;1-5(2,3)4;/h4,6,9H,1-3,5,7,23H2;(H3,1,2,3,4);1H2/t9-;;/m1../s1
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| Chemical Name |
(3R)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;phosphoric acid;hydrate
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| Synonyms |
MK 431; Sitagliptin Phosphate; MK-0431; MK0431; MK 0431; Sitagliptin Phosphate Monohydrate; MK-431; MK431; trade name: Januvia Xelevia Janumet
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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 |
| 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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9109 mL | 9.5544 mL | 19.1088 mL | |
| 5 mM | 0.3822 mL | 1.9109 mL | 3.8218 mL | |
| 10 mM | 0.1911 mL | 0.9554 mL | 1.9109 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00944450 | Completed | Drug: Sitagliptin phosphate anhydrous formulation Drug: Comparator: sitagliptin phosphate monohydrate form |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | August 2004 | Phase 1 |
| NCT01785043 | Completed | Drug: Liraglutide Drug: Sitagliptin |
DIABETES Mellitus Type 2 Not Well Controlled |
Anna Cruceta | March 2013 | Phase 4 |
| NCT01062048 | Completed | Drug: Sitagliptin Drug: Sulfonylurea |
Type 2 Diabetes Mellitus | Merck Sharp & Dohme LLC | October 2008 |
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