Sitagliptin phosphate
Based on 31 publication(s) in Google Scholar
Sitagliptin (MK-0431) 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.
For research use only. We do not sell to patients.
- Purity: 99.88%
- CAS No.: 654671-78-0
- Formula: C16H18F6N5O5P
- Molecular Weight:505.31
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Storage:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Publications Citing Use of MedChemExpress (MCE) Sitagliptin phosphate
More- J Adv Res. 2025 Aug:74:225-236. [Abstract]
- J Nanobiotechnology. 2024 Oct 16;22(1):631. [Abstract]
- Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
- Cell Death Dis. 2021 Oct 11;12(10):928. [Abstract]
- Int J Biol Macromol. 2025 Jun 6;318(Pt 1):145051. [Abstract]
- Biomed Pharmacother. 2023 Jun:162:114555. [Abstract]
- Biochem Pharmacol. 2023 Nov:217:115846. [Abstract]
- J Ethnopharmacol. 2025 Sep 9;355(Pt A):120587. [Abstract]
- World J Diabetes. 2025 Jun 15;16(6):103616. [Abstract]
- Mol Oncol. 2025 Dec 21. [Abstract]
- Biochim Biophys Acta Mol Basis Dis. 2024 Jul 25:167433. [Abstract]
- iScience. 2023 Feb 27;26(3):106271. [Abstract]
- Sci Rep. 2019 Mar 11;9(1):4074. [Abstract]
- Nutr Neurosci. 2019 Dec;22(12):877-893. [Abstract]
- Exp Cell Res. 2024 Sep 12;442(2):114254. [Abstract]
- Life Metab. 2025 Feb 8;4(2):loaf004. [Abstract]
- Front Oncol. 2021 Sep 24:11:728047. [Abstract]
- Nutrition. 2024 Dec:128:112565. [Abstract]
- 3 Biotech. 2026 Apr;16(4):146. [Abstract]
- J Sep Sci. 2022 Jan;45(2):631-637. [Abstract]
- BMC Pharmacol Toxicol. 2025 Dec 8;26(1):208. [Abstract]
- Tissue Cell. 2026 Jun 17:103:103704. [Abstract]
- Korean J Physiol Pharmacol. 2021 Sep 1;25(5):425-437. [Abstract]
- Arch Oral Biol. 2025 Jul:175:106253. [Abstract]
- Neurol Res. 2018 Sep;40(9):736-743. [Abstract]
- bioRxiv. 2026 Feb 12:2026.02.10.705129. [Abstract]
- Orebro University. 2024.
- Research Square Preprint. 2024 Apr 25.
- bioRxiv. 2023 Nov 4.
- Oxid Med Cell Longev. 2022 May 17;2022:2586305. [Abstract]
- Oxid Med Cell Longev. 2019 Nov 15;2019:6181754. [Abstract]
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In Vivo Efficacy Study
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Histological Imaging/Staining
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Histological Imaging/Staining
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IF
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RT-PCR
All Endogenous Metabolite Isoforms
More
Biological Activity
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DPP-4 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
11 μM
Compound: MK-0431
|
Inhibition of human DPP8 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
Inhibition of human DPP8 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
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[PMID: 22853995] |
| HEK293 | IC50 |
20 μM
Compound: MK-0431
|
Inhibition of human DPP9 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
Inhibition of human DPP9 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
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[PMID: 22853995] |
| HEK293 | IC50 |
22 nM
Compound: Sitagliptin Phosphate
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Inhibition of recombinant human DPP-4 expressed in HEK293 cells using H-Gly-Pro-AMC as substrate measured over 15 mins by fluorescence analysis
Inhibition of recombinant human DPP-4 expressed in HEK293 cells using H-Gly-Pro-AMC as substrate measured over 15 mins by fluorescence analysis
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[PMID: 28128944] |
| HEK293 | IC50 |
6 nM
Compound: MK-0431
|
Inhibition of human DPP4 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
Inhibition of human DPP4 expressed in HEK293 cells using Ala-Pro-p-nitroanilide hydrochloride salt as substrate preincubated for 10 mins prior to addition of substrate measured after 30 mins
|
[PMID: 22853995] |
Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50 of 19 nM from Caco-2 cell extracts[1]. Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involving cAMP/PKA/Rac1 activation[2]. A recent study demonstrates that sitagliptin exerts a novel, direct action in order to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 654671-78-0
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Appearance Solid
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Molecular Weight 505.31
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Formula C16H18F6N5O5P
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Color White to off-white
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SMILES
O=C(N1CC2=NN=C(C(F)(F)F)N2CC1)C[C@H](N)CC3=CC(F)=C(F)C=C3F.O=P(O)(O)O
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Synonyms
MK-0431 phosphate
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Publications (31)
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Journal Impact Factor
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Most Recent
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J Adv Res
Hippocampal dipeptidyl peptidase 9 bidirectionally regulates memory associated with synaptic plasticity. [Abstract]2025 Aug:74:225-236. PMID: 39369958 -
J Nanobiotechnology
Metal-organic-framework-based sitagliptin-release platform for multieffective radiation-induced intestinal injury targeting therapy and intestinal flora protective capabilities. [Abstract]2024 Oct 16;22(1):631. PMID: 39415273 -
Gut Microbes
Dual-source DPP4 drives intestinal fibrosis in Crohn's disease: synergistic therapeutic targeting of host and microbiota pathways. [Abstract]2025 Dec 31;17(1):2593119. PMID: 41334589
Sitagliptin phosphate purchased from MedChemExpress. Usage Cited in: Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
Colon length quantification in the DSS group (n = 6) and DSS + DPP4i group (n = 6). Mice received three cycles of 1.5% DSS (7 days per cycle), each followed by a 14-day recovery phase. The DPP4 inhibitor sitagliptin was administered via oral gavage for 21 days during the final cycle of the experiment.
Sitagliptin phosphate purchased from MedChemExpress. Usage Cited in: Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
Representative H&E-stained colon sections (left) and histologic inflammation scores (right). Mice received three cycles of 1.5% DSS (7 days per cycle), each followed by a 14-day recovery phase. The DPP4 inhibitor sitagliptin was administered via oral gavage for 21 days during the final cycle of the experiment.
Sitagliptin phosphate purchased from MedChemExpress. Usage Cited in: Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
Representative Masson’s trichrome-stained colon sections and quantification of collagen volume fraction. Mice received three cycles of 1.5% DSS (7 days per cycle), each followed by a 14-day recovery phase. The DPP4 inhibitor sitagliptin was administered via oral gavage for 21 days during the final cycle of the experiment.
Sitagliptin phosphate purchased from MedChemExpress. Usage Cited in: Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
Immunofluorescence images and quantification of α-SMA⁺ fibrotic thickness in the muscularis propria. Mice received three cycles of 1.5% DSS (7 days per cycle), each followed by a 14-day recovery phase. The DPP4 inhibitor sitagliptin was administered via oral gavage for 21 days during the final cycle of the experiment.
Sitagliptin phosphate purchased from MedChemExpress. Usage Cited in: Gut Microbes. 2025 Dec 31;17(1):2593119. [Abstract]
RT-qPCR analysis of mRNA levels in colon tissues. Mice received three cycles of 1.5% DSS (7 days per cycle), each followed by a 14-day recovery phase. The DPP4 inhibitor sitagliptin was administered via oral gavage for 21 days during the final cycle of the experiment.
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Cell Death Dis
Sitagliptin activates the p62-Keap1-Nrf2 signalling pathway to alleviate oxidative stress and excessive autophagy in severe acute pancreatitis-related acute lung injury. [Abstract]2021 Oct 11;12(10):928. PMID: 34635643 -
Int J Biol Macromol
Comprehending the mechanism of catechins against α-glucosidase by multispectral data and their antidiabetic effects in vivo. [Abstract]2025 Jun 6;318(Pt 1):145051. PMID: 40484085 -
Biomed Pharmacother
Sitagliptin inhibits the survival, stemness and autophagy of glioma cells, and enhances temozolomide cytotoxicity. [Abstract]2023 Jun:162:114555. PMID: 36966667 -
Biochem Pharmacol
Melatonin protects HT-22 cells against palmitic acid-induced glucolipid metabolic dysfunction and cell injuries: Involved in the regulation of synaptic plasticity and circadian rhythms. [Abstract]2023 Nov:217:115846. PMID: 37804870 -
J Ethnopharmacol
Eucommia alleviates high fat diet-induced MASLD via the F. prausnitzii/butyrate/GPR43/GLP-1 signaling. [Abstract]2025 Sep 9;355(Pt A):120587. PMID: 40935212 -
World J Diabetes
Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretion via inhibiting farnesoid X receptor. [Abstract]2025 Jun 15;16(6):103616. PMID: 40548276 -
Mol Oncol
2025 Dec 21. PMID: 41422479 -
Biochim Biophys Acta Mol Basis Dis
Dapagliflozin attenuates AKI to CKD transition in diabetes by activating SIRT3/PGC1-α signaling and alleviating aberrant metabolic reprogramming. [Abstract]2024 Jul 25:167433. PMID: 39067538 -
iScience
Non-canonical function of DPP4 promotes cognitive impairment through ERp29-associated mitochondrial calcium overload in diabetes. [Abstract]2023 Feb 27;26(3):106271. PMID: 36936785 -
Sci Rep
2019 Mar 11;9(1):4074. PMID: 30858459 -
Nutr Neurosci
High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome. [Abstract]2019 Dec;22(12):877-893. PMID: 29697017 -
Exp Cell Res
SOX9 promotes hypoxic pulmonary hypertension through stabilization of DPP4 in pulmonary artery smooth muscle cells. [Abstract]2024 Sep 12;442(2):114254. PMID: 39276964 -
Life Metab
Development of cyclopeptide inhibitors specifically disrupting FXR-coactivator interaction in the intestine as a novel therapeutic strategy for MASH. [Abstract]2025 Feb 8;4(2):loaf004. PMID: 40225300 -
Front Oncol
Antidiabetic DPP-4 Inhibitors Reprogram Tumor Microenvironment That Facilitates Murine Breast Cancer Metastasis Through Interaction With Cancer Cells via a ROS-NF-кB-NLRP3 Axis. [Abstract]2021 Sep 24:11:728047. PMID: 34631556 -
Nutrition
Lactobacillus plantarum NCHBL-004 modulates high-fat diet-induced weight gain and enhances GLP-1 production for blood glucose regulation. [Abstract]2024 Dec:128:112565. PMID: 39326237 -
3 Biotech
Neuroprotective effects of DPP-4 inhibitors sitagliptin and vildagliptin in Parkinson's disease via autophagy modulation. [Abstract]2026 Apr;16(4):146. PMID: 41853215 -
J Sep Sci
High-throughput bioanalysis of sitagliptin in plasma using direct analysis in real time mass spectrometry and its application in the pharmacokinetic study thereof. [Abstract]2022 Jan;45(2):631-637. PMID: 34709732 -
BMC Pharmacol Toxicol
Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma. [Abstract]2025 Dec 8;26(1):208. PMID: 41361888 -
Tissue Cell
Saligenin restores insulin responsiveness in lipotoxic myotubes through L-cell-derived GLP-1 via ER stress-autophagy modulation. [Abstract]2026 Jun 17:103:103704. PMID: 42320358 -
Korean J Physiol Pharmacol
Sitagliptin attenuates endothelial dysfunction independent of its blood glucose controlling effect. [Abstract]2021 Sep 1;25(5):425-437. PMID: 34448460 -
Arch Oral Biol
Sitagliptin regulates the AMPK/NF-κB signaling pathway to alleviate lipopolysaccharide-induced inflammatory responses and promote osteogenic differentiation in rat bone marrow mesenchymal stem cells. [Abstract]2025 Jul:175:106253. PMID: 40215713 -
Neurol Res
Sitagliptin rescues memory deficits in Parkinsonian rats via upregulating BDNF to prevent neuron and dendritic spine loss. [Abstract]2018 Sep;40(9):736-743. PMID: 29781786 -
bioRxiv
Characterizing the SASP-Dependent Paracrine Spreading of Senescence Between Human Brain Cell Types. [Abstract]2026 Feb 12:2026.02.10.705129. PMID: 41726875 -
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Oxid Med Cell Longev
Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder. [Abstract]2022 May 17;2022:2586305. PMID: 35620578 -
Oxid Med Cell Longev
DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling. [Abstract]2019 Nov 15;2019:6181754. PMID: 31827684
Solvent & Solubility
DMSO : 100 mg/mL (197.90 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 50 mg/mL (98.95 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.95 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.95 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 50 mg/mL (98.95 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocol
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice: Overnight fasted C57BL/6J mice are challenged 45 min after compound administration with an oral glucose load (2 g/kg). Blood samples for glucose measurement are obtained by tail bleed predose and at serial time points after the glucose load. To evaluate the duration of the effect on glucose tolerance, vehicle or DPP-4 inhibitors are administered 16 h before the glucose challenge.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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 [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
[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. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O / DMSO | 1 mM | 1.9790 mL | 9.8949 mL | 19.7898 mL | 49.4746 mL |
| 5 mM | 0.3958 mL | 1.9790 mL | 3.9580 mL | 9.8949 mL | |
| 10 mM | 0.1979 mL | 0.9895 mL | 1.9790 mL | 4.9475 mL | |
| 15 mM | 0.1319 mL | 0.6597 mL | 1.3193 mL | 3.2983 mL | |
| 20 mM | 0.0989 mL | 0.4947 mL | 0.9895 mL | 2.4737 mL | |
| 25 mM | 0.0792 mL | 0.3958 mL | 0.7916 mL | 1.9790 mL | |
| 30 mM | 0.0660 mL | 0.3298 mL | 0.6597 mL | 1.6492 mL | |
| 40 mM | 0.0495 mL | 0.2474 mL | 0.4947 mL | 1.2369 mL | |
| 50 mM | 0.0396 mL | 0.1979 mL | 0.3958 mL | 0.9895 mL | |
| 60 mM | 0.0330 mL | 0.1649 mL | 0.3298 mL | 0.8246 mL | |
| 80 mM | 0.0247 mL | 0.1237 mL | 0.2474 mL | 0.6184 mL | |
| DMSO | 100 mM | 0.0198 mL | 0.0989 mL | 0.1979 mL | 0.4947 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.