Sitagliptin-phosphate-monohydrate-MK-0431-phosphate-monohydrate-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESitagliptin phosphate monohydrateCat. No.: HY-13749BCAS No.: 654671-77-9Synonyms: MK-0431 phosphate monohydrate分式: CHFNOP分量: 523.32作靶點(diǎn): Dipeptidyl Peptidase; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy儲存式: Powder -20C 3 y

2、ears4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 33 mg/mL (63.06 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.9109 mL 9.5544 mL 19.1088 mL5 mM 0.3822 mL 1.9109 mL 3.8218 mL10 mM 0.1911 mL 0.9554 mL 1.9109 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制

3、儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Sitagliptin(MK 0431)DPP4效抑制劑，在Caco-2細(xì)胞中IC50值為19nM。IC50 & Target IC50: 19 nM (DPP4, in Caco-2 cell extracts)體外研究Sitagliptin phosphate exhibits a potent inhibitory effect on DPP-4 with IC50 of 19 nM from Caco-2 cell1/3 Master of Small Molecules 您邊的抑制劑師www.MedC

4、hemEextracts 1. Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involvingcAMP/PKA/Rac1 activation 2. A recent study demonstrates that sitagliptin exerts a novel, direct action inorder to stimulate GLP-1 secretion by the intestinal L cell through a DPP-4-indep

5、endent, protein kinase A-and MEK-ERK1/2-dependent pathway. It therefore reduces the effect of autoimmunity on graft survival 3.體內(nèi)研究 In vivo, the ED50 value of sitagliptin phosphate for inhibition of plasma DPP-4 activity is calculated to be 2.3mg/kg 7 hour postdose and 30 mg/kg 24 hour postdose in f

6、reely fed Han-Wistar rats 1. The streptozotocin-induced type 1 diabetes mouse model exhibits elevated DPP-4 levels in the plasma that can be substantiallyinhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation ofhyperglycemia, potentially through p

7、rolongation of islet graft survival 4. The plasma clearance and volumeof distribution of Sitagliptin phosphate are higher in rats (40-48 mL/min/kg, 7-9 L/kg) than in dogs (9mL/min/kg, 3 L/kg); and its half-life is shorter in rats,2 hours compared with 4 hours in dogs 5.PROTOCOLKinase Assay 1 DPP-4 i

8、s extracted from confluent Caco-2 cells. After 5 minutes of incubation at room temperature with lysisbuffer (10 mM Tris-HCl, 150 mM NaCl, 0.04 U/mL aprotinin, 0.5% Nonidet P40, pH 8.0), cells are centrifugedat 35,000 g at 4C for 30 minutes, and the supernatant is stored at -80C. Assays are performed

9、 by mixing20 L of appropriate compound dilutions with 50 L of the substrate for the DPP-4 enzyme, H-Ala-Pro-7-amido-4-trifluoromethylcoumarin (final concentration in the assay, 100 M) and 30 L of the Caco-2 cellextract (diluted 1000-fold with 100 mM Tris-HCl, 100 mM NaCl, pH 7.8). Plates are incubat

10、ed at roomtemperature for 1 hour, and fluorescence is measured at excitation/emission wavelengths of 405/535 nmusing a SpectraMax GeminiXS. Dissociation kinetics of inhibitors from the DPP-4 enzyme is determined aftera 1-hour preincubation of Caco-2 cell extracts with high inhibitor concentrations (

11、30 nM for BI 1356, 3 M forvildagliptin). 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 theseconditions, the difference in DPP-4 activity at a certain time point in

12、 the presence or absence of an inhibitorreflects the amount of this inhibitor still bound to the DPP-4 enzyme. Maximal reaction rates (fluorescenceunits/seconds 1000) at 10-minute intervals are calculated using the SoftMax software of the SpectraMaxand corrected for the rate of an uninhibited reacti

13、on (vcontrol-vinhibitor)/vcontrol.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 CD4T-cells are plated on membrane inserts in serum-free RPMI 1640, and cell migration is assayed usingTranswell chambers (Corning), in the presence or absence

14、 of purified porcine kidney DPP-4 (32.1 units/mg;100 mU/mL final concentration) and DPP-4 inhibitor (100 M). After 1 hour, cells on the upper surface areremoved mechanically, and cells that have migrated into the lower compartment are counted. The extent ofmigration is expressed relative to the cont

15、rol sample.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Overnight fasted C57BL/6J mice are challenged 45 min after compound administration with an oralAdministration 1 glucose load (2 g/kg). Blood samples for glucose measurement are obta

16、ined by tail bleed predose and atserial time points after the glucose load. To evaluate the duration of the effect on glucose tolerance, vehicleor DPP-4 inhibitors are administered 16 h before the glucose challenge.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE has not independently confirmed

17、the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Biol Chem. 2018 Dec 7;293(49):18864-18878. Sci Rep. 2019 Mar 11;9(1):4074. Nutr Neurosci. 2018 Apr 26:1-17. Neurol Res. 2018 Sep;40(9):736-743.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Thomas, L., et

18、 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 acti2. Kim, S.J., et al., Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cellmodulation. Diabetes, 2009. 58(3): p. 641-51.3. Sangle, G.V., et al., Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a