Sitagliptin-phosphate-monohydrate-MK-0431-phosphate-monohydrate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemESitagliptinphosphatemonohydrateCat.No.:HY-13749BCASNo.:654671-77-9Synonyms:MK-0431phosphatemonohydrate分⼦式:C₁₆H₂₀F₆N₅O₆P分⼦量:523.32作⽤靶点:DipeptidylPeptidase;Autophagy作⽤通路:MetabolicEnzyme/Protease;Autophagy储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验H2O:≥33mg/mL(63.06mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9109mL9.5544mL19.1088mL5mM0.3822mL1.9109mL3.8218mL10mM0.1911mL0.9554mL1.9109mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：PBS1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:50mg/mL(95.54mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Sitagliptin(MK0431phosphatemonohydrate)⼀种有效的DPP4抑制剂，在Caco-2细胞中，IC50值为19nM[1]。IC50&TargetIC50:19nM(DPP4,inCaco-2cellextracts)体外研究SitagliptinphosphateexhibitsapotentinhibitoryeffectonDPP-4withIC50of19nMfromCaco-2cellextracts[1].SitagliptinreducesinvitromigrationofisolatedsplenicCD4T-cellsthroughapathwayinvolvingcAMP/PKA/Rac1activation[2].Arecentstudydemonstratesthatsitagliptinexertsanovel,directactioninordertostimulateGLP-1secretionbytheintestinalLcellthroughaDPP-4-independent,proteinkinaseA-andMEK-ERK1/2-dependentpathway.Itthereforereducestheeffectofautoimmunityongraftsurvival[3].体内研究Invivo,theED50valueofsitagliptinphosphateforinhibitionofplasmaDPP-4activityiscalculatedtobe2.3mg/kg7hourpostdoseand30mg/kg24hourpostdoseinfreelyfedHan-Wistarrats[1].Thestreptozotocin-inducedtype1diabetesmousemodelexhibitselevatedDPP-4levelsintheplasmathatcanbesubstantiallyinhibitedinmiceonanSitagliptinphosphatediet.Thisisachievedbyapositiveeffectontheregulationofhyperglycemia,potentiallythroughprolongationofisletgraftsurvival[4].TheplasmaclearanceandvolumeofdistributionofSitagliptinphosphatearehigherinrats(40-48mL/min/kg,7-9L/kg)thanindogs(9mL/min/kg,3L/kg);anditshalf-lifeisshorterinrats,2hourscomparedwith4hoursindogs[5].PROTOCOLCellAssay[2]CD4T-cellsareplatedonmembraneinsertsinserum-freeRPMI1640,andcellmigrationisassayedusingTranswellchambers(Corning),inthepresenceorabsenceofpurifiedporcinekidneyDPP-4(32.1units/mg;100mU/mLfinalconcentration)andDPP-4inhibitor(100μM).After1hour,cellsontheuppersurfaceareremovedmechanically,andcellsthathavemigratedintothelowercompartmentarecounted.Theextentofmigrationisexpressedrelativetothecontrolsample.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:OvernightfastedC57BL/6Jmicearechallenged45minaftercompoundadministrationwithanoralAdministration[1]glucoseload(2g/kg).Bloodsamplesforglucosemeasurementareobtainedbytailbleedpredoseandatserialtimepointsaftertheglucoseload.Toevaluatethedurationoftheeffectonglucosetolerance,vehicleorDPP-4inhibitorsareadministered16hbeforetheglucosechallenge.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellDeathDis.2021Oct11;12(10):928.•OxidMedCellLongev.2022May17;2022:2586305.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•OxidMedCellLongev.2019Nov15;2019:6181754.•FrontOncol.24September2021.•JBiolChem.2018Dec7;293(49):18864-18878.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Thomas,L.,etal.(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(BI1356),anovelxanthine-baseddipeptidylpeptidase4inhibitor,hasasuperiorpotencyandlongerdurationofacti[2].Kim,S.J.,etal.,DipeptidylpeptidaseIVinhibitionwithMK0431improvesisletgraftsurvivalindiabeticNODmicepartiallyviaT-cellmodulation.Diabetes,2009.58(3):p.641-51.[3].Sangle,G.V.,etal.,Novelbiologicalactionofthedipeptidylpeptidase-IVinhibitor,sitagliptin,asaGLP-1secretagogue.Endocrinology,2012.153(2):p.564-73.[4].Kim,S.J.,etal.,InhibitionofdipeptidylpeptidaseIVwithsitagliptin(MK0431)prolongsisletgraftsurvivalinstreptozotocin-induceddiabeticmice.Diabetes,2008.57(5):p.1331-9.[5].Beconi,M.G.,etal.Dispositionofthedipeptidylpeptidase4inhibitorsitagliptininratsanddogs.D