Sitagliptin phosphate monohydrate

Name: Sitagliptin phosphate monohydrate
Brand: Selleck Chemicals
SKU: S4002
Rating: 5 (3 reviews)

For research use only.

Catalog No.S4002 Synonyms: MK-0431

3 publications

Sitagliptin phosphate monohydrate Chemical Structure

Molecular Weight(MW): 523.32

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

Selleck's Sitagliptin phosphate monohydrate has been cited by 3 publications

Circulation, 2017, 135(20):1935-1950

PubMed: 28179397 ( click the link to review the publication )

Psychoneuroendocrinology, 2015, 53, 195-206

PubMed: 25635612 ( click the link to review the publication )

Sci Rep, 2013, 3:2104

PubMed: 23812503 ( click the link to review the publication )

2 Customer Reviews

Functional lack of DPP4 activity was confirmed in plasma samples from DPP4mut rats, as compared to DAwt (E, white and dark bars) and to rats treated with sitagliptin for three weeks (E, light gray bars). Specificity of the assay was further confirmed by inhibition of the measured peptidase activity with sitagliptin, in vitro.

Psychoneuroendocrinology, 2015, 53:195—206. Sitagliptin phosphate monohydrate purchased from Selleck.

AR staining of non-CAVD and CAVD patient hVICs in the presence or absence of Sitagliptin (100 μM) after 4 weeks of osteogenic stimulation. The bar graph presents the AR-positive area measured in each culture dish.

Circulation, 2017, 135(20):1935-1950. Sitagliptin phosphate monohydrate purchased from Selleck.

Purity & Quality Control

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Biological Activity

Description

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

Features

A potent, orally active inhibitor of DPP-4.

Targets

DPP-4 ^[1]
(Cell-free assay)

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]

Protocol

Kinase Assay:^[1]	- Collapse 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 Research:^[2]	- Collapse 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. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: Freely fed Han-Wistar rats Dosages: ≤10 mg/kg Administration: Administered via p.o. (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	100 mg/mL (191.08 mM)
	Water	41 mg/mL (78.34 mM)
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): Saline For best results, use promptly after mixing.	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.

Chemical Information Download Sitagliptin phosphate monohydrate SDF Download Sitagliptin phosphate monohydrate SDF

Molecular Weight	523.32
Formula	C₁₆H₁₅F₆N₅O.H₃PO₄.H₂O
CAS No.	654671-77-9
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	MK-0431
Smiles	O.NC(CC(=O)N1CC[N]2C(=NN=C2C(F)(F)F)C1)CC3=C(F)C=C(F)C(=C3)F.O[P](O)(O)=O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

Serial Dilutions
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Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
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C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-05-15)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03359590	Completed	Drug: Sitagliptin 100mg\|Other: Placebo arm	Pharmacological Action	Profil Institut für Stoffwechselforschung GmbH\|Merck Sharp & Dohme Corp.	March 21 2018	Phase 2
NCT03659461	Recruiting	Drug: Sitagliptin	Type 2 Diabetes Mellitus\|PreDiabetes	National University of Malaysia	October 1 2017	Not Applicable
NCT03233178	Completed	Other: Non-interventional	T2DM (Type 2 Diabetes Mellitus)\|Fatty Liver\|NAFLD	LMC Diabetes & Endocrinology Ltd.	January 2017	--
NCT02900417	Unknown status	Drug: Sitagliptin	Type 2 Diabetes	Second Affiliated Hospital of Soochow University	September 2016	Not Applicable

Tech Support

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.

Handling Instructions

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Sitagliptin phosphate monohydrate