Sitagliptin-MK0431-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESitagliptinCat. No.: HY-13749CAS No.: 486460-32-6Synonyms: MK0431分式: CHFNO分量: 407.31作靶点: Dipeptidyl Peptidase; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 mo

2、nth溶解性数据体外实验 DMSO : 50 mg/mL (122.76 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.4551 mL 12.2757 mL 24.5513 mL5 mM 0.4910 mL 2.4551 mL 4.9103 mL10 mM 0.2455 mL 1.2276 mL 2.4551 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案

3、，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.14 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.14 mM); Clear solutio

4、n1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.14 mM); Clear solution; Need heat to 60CBIOLOGICAL ACTIVITY物活性 Sitagliptin种有效的 DPP4 抑制剂，在 Caco-2 细胞中，IC50 值为 19 nM。IC50 & Target IC50: 19 nM (DPP4) 1体外研究 Sitagliptin phosphate exhibits a pot

5、ent inhibitory effect on DPP-4 with IC50 of 19 nM from Caco-2 cellextracts 1. Sitagliptin reduces in vitro migration of isolated splenic CD4 T-cells through a pathway involvingcAMP/PKA/Rac1 activation 2. Stagliptin exerts a novel, direct action in order to stimulate GLP-1 secretionby the intestinal

6、L cell through a DPP-4-independent, protein kinase A- and MEK-ERK1/2-dependentpathway. It reduces the effect of autoimmunity on graft survival 3.体内研究 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

7、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 substantiallyinhibited in mice on an Sitagliptin phosphate diet. This is achieved by a positive effect on the regulation ofhyperglycemia, pot

8、entially through prolongation 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.PROTOCOLKina

9、se Assay 1 DPP-4 is 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. As

10、says are performed 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).

11、Plates are incubated 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 inhibito

12、r concentrations (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 cer

13、tain time point in 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

14、uninhibited reaction (vcontrol-vinhibitor)/vcontrol.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemECell Assay 2 CD4T-cells are plated on membrane inserts in serum-free RPMI 1640, and cell migration is as

15、sayed usingTranswell 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 M). After 1 hour, cells on the upper surface areremoved mechanically, and cells that have migrated into the lower compartment ar

16、e counted. The extent ofmigration is expressed relative to the control 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 gl

17、ucose load (2 g/kg). Blood samples for glucose measurement are obtained 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.MCE has not indepe

18、ndently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 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.MedChemEREFERENCE

19、S1. Thomas, L., et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-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 action compared with otherdipeptidyl peptidase-

20、4 inhibitors. J Pharmacol Exp Ther. 2008 Apr;325(1):175-82.2. 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 dipeptidy