Sitagliptin phosphate monohydrate

Catalog No.S4002 1 Product Citations

Sitagliptin phosphate is a potent inhibitor of DPP-IV with IC50 of 19 nM in Caco-2 cell extracts.

Price Stock Quantity  
In DMSO USD 120 In stock
USD 90 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Sitagliptin phosphate monohydrate Chemical Structure

Sitagliptin phosphate monohydrate Chemical Structure
Molecular Weight: 523.32

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

Sitagliptin phosphate monohydrate is available in the following compound libraries:

Product Information

  • Compare DPP-4 Inhibitors
    Compare DPP-4 Products
  • Research Area

Product Description

Biological Activity

Description Sitagliptin phosphate is a potent inhibitor of DPP-IV with IC50 of 19 nM in Caco-2 cell extracts.
Targets DPP-4 [1]
IC50 19 nM
In vitro As an orally active agent, Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50 of 19 nM from Caco-2 cell extracts. [1] MK0431 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]
In vivo In vivo, the ED50 value of Sitagliptin phosphate for inhibition of plasma DPP-4 activity is calculated to be 2.3 mg/kg 7 hour postdose and 30 mg/kg 24 hour postdose in freely fed Han-Wistar rats. [1] The streptozotocin-induced type 1 diabetes mouse model exhibits elevated DPP-4 levels in the plasma that can be substantially inhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation of hyperglycemia, potentially through prolongation of islet graft survival. [4] The plasma clearance and volume of distribution of Sitagliptin phosphate are higher in rats (40-48 mL/min/kg, 7-9 L/kg) than in dogs (9 mL/min/kg, 3 L/kg); and its half-life is shorter in rats,2 hours compared with 4 hours in dogs. [5]
Features A potent, orally active inhibitor of DPP-4.

Protocol(Only for Reference)

Kinase Assay: [1]

Plasma DPP-4 Activity[2] DPP-4 is extracted from confluent Caco-2 cells. After 5 minutes of incubation at room temperature with lysis buffer (10 mM Tris-HCl, 150 mM NaCl, 0.04 U/mL aprotinin, 0.5% Nonidet P40, pH 8.0), cells are centrifuged at 35,000 g at 4 °C for 30 minutes, and the supernatant is stored at -80°C. Assays are performed by mixing 20 μL of appropriate compound dilutions with 50 μL of the substrate for the DPP-4 enzyme, H-Ala-Pro-7-amido-4-trifluoromethylcoumarin (final concentration in the assay, 100 μM) and 30 μL of the Caco-2 cell extract (diluted 1000-fold with 100 mM Tris-HCl, 100 mM NaCl, pH 7.8). Plates are incubated at room temperature for 1 hour, and fluorescence is measured at excitation/emission wavelengths of 405/535 nm using a SpectraMax GeminiXS. Dissociation kinetics of inhibitors from the DPP-4 enzyme is determined after a 1-hour preincubation of Caco-2 cell extracts with high inhibitor concentrations (30 nM for BI 1356, 3 μM for vildagliptin). The enzymatic reaction is started by adding the substrate H-Ala-Pro-7-amido-4-trifluoromethylcoumarin after a 3000-fold dilution of the preincubation mixture with assay buffer. Under these conditions, the difference in DPP-4 activity at a certain time point in the presence or absence of an inhibitor reflects the amount of this inhibitor still bound to the DPP-4 enzyme. Maximal reaction rates (fluorescence units/seconds × 1000) at 10-minute intervals are calculated using the SoftMax software of the SpectraMax and corrected for the rate of an uninhibited reaction [(vcontrol-vinhibitor)/vcontrol].

Cell Assay: [2]

Cell lines CD4 T-cells
Concentrations 100 μM
Incubation Time 1 hour
Method 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.

Animal Study: [1]

Animal Models Freely fed Han-Wistar rats
Formulation 0.5% aqueous hyroxyethylcellulose.
Dosages ≤10 mg/kg
Administration Administered via p.o.
Solubility Saline, 30 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Thomas L et al. J Pharmacol Exp Ther. 2008; 325(1): 175-182.

[2] Kim SJ et al. Diabetes. 2009; 58(3): 641-651.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-11-22)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01824264 Withdrawn Type 2 Diabetes Mellitus Novartis Pharmaceuticals|Novartis November 2015 Phase 2
NCT01984606 Withdrawn Diabetes Mellitus, Type 2 Boehringer Ingelheim|Eli Lilly and Company January 2015 Phase 3
NCT02284893 Not yet recruiting Type 2 Diabetes Bristol-Myers Squibb|AstraZeneca December 2014 Phase 3
NCT02122380 Not yet recruiting Polycystic Ovary Syndrome Vanderbilt University|National Heart, Lung, and Blood Ins  ...more Vanderbilt University|National Heart, Lung, and Blood Institute (NHLBI) December 2014 Phase 0
NCT02294084 Not yet recruiting Neoplasms, Adipose Tissue IngridJazet|Merck Sharp & Dohme Corp.|Leiden University M  ...more IngridJazet|Merck Sharp & Dohme Corp.|Leiden University Medical Center December 2014 Phase 4

view more

Chemical Information

Download Sitagliptin phosphate monohydrate SDF
Molecular Weight (MW) 523.32
Formula

C16H15F6N5O.H3PO4.H2O

CAS No. 654671-77-9
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms MK-0431
Solubility (25°C) * In vitro DMSO 100 mg/mL (191.08 mM)
Water 41 mg/mL (78.34 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo Saline 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one phosphate monohydrate

Research Area

Product Citations (1)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related DPP-4 Products

  • Trelagliptin

    Trelagliptin is a highly selective, long-acting DPP-4 inhibitor. Phase 3.

  • E-64

    E-64 is an irreversible and selective cysteine protease inhibitor with IC50 of 9 nM for papain.

  • AEBSF HCl

    AEBSF HCl is a broad spectrum, irreversible serine protease inhibitor.

  • Glimepiride

    Glimepiride is a medium-to-long acting sulfonylurea anti-diabetic compound with an ED50 of 182 μg/kg.

  • Saxagliptin

    Saxagliptin is a selective and reversible DPP4 inhibitor with IC50 of 26 nM.

  • Linagliptin

    Linagliptin is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM.

  • Vildagliptin (LAF-237)

    Vildagliptin (LAF-237) inhibits DPP−4 with IC50 of 2.3 nM.

  • Alogliptin

    Alogliptin is a potent, selective inhibitor of DPP-4 with IC50 of <10 nM, exhibits greater than 10,000-fold selectivity over DPP-8 and DPP-9.

  • MG-132

    MG-132 is an inhibitor of proteasome with IC50 of 100 nM, and also inhibits calpain with IC50 of 1.2 μM.

  • Bortezomib (PS-341)

    Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM.

Recently Viewed Items

Tags: buy Sitagliptin phosphate monohydrate | Sitagliptin phosphate monohydrate ic50 | Sitagliptin phosphate monohydrate price | Sitagliptin phosphate monohydrate cost | Sitagliptin phosphate monohydrate solubility dmso | Sitagliptin phosphate monohydrate purchase | Sitagliptin phosphate monohydrate manufacturer | Sitagliptin phosphate monohydrate research buy | Sitagliptin phosphate monohydrate order | Sitagliptin phosphate monohydrate mouse | Sitagliptin phosphate monohydrate chemical structure | Sitagliptin phosphate monohydrate mw | Sitagliptin phosphate monohydrate molecular weight | Sitagliptin phosphate monohydrate datasheet | Sitagliptin phosphate monohydrate supplier | Sitagliptin phosphate monohydrate in vitro | Sitagliptin phosphate monohydrate cell line | Sitagliptin phosphate monohydrate concentration | Sitagliptin phosphate monohydrate nmr
Contact Us