PIK-75-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPIK-75Cat.No.:HY-107834CASNo.:372196-67-3分⼦式:C₁₆H₁₄BrN₅O₄S分⼦量:452.28作⽤靶点:DNA-PK;PI3K;Apoptosis作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性PIK-75⼀种可逆的DNA-PK和p110α-选择性的抑制剂，抑制DNA-PK，p110α和p110γ，IC50分别为2，5.8和76nM。PIK-75抑制p110α效果⽐抑制p110β(IC50=1.3μM)⾼200多倍[1][2]。PIK-75诱导凋亡(apoptosis)[3]。IC50&Targetp110αp110γp110δp110β5.8nM(IC50)76nM(IC50)510nM(IC50)1.3μM(IC50)hsVPS34PI3KC2βPI3KC2αPI4KIIIβ2.6μM(IC50)1μM(IC50)10μM(IC50)50μM(IC50)ATMATRmTORC1mTORC22.3μM(IC50)21μM(IC50)1μM(IC50)10μM(IC50)DNA-PK2nM(IC50)体外研究PIK-75alsoinhibitsp110δ,PI3KC2β,mTORC1,ATM,hsVPS34,PI3KC2α,mTORC2,ATRandPI4KIIIβwithIC50sof510nM,~1μM,~1μM,2.3μM,2.6μM,~10μM,~10μM,21μM,~50μM,respectively[1].PIK-75aloneblocksThr308phosphorylationinL6myotubesand3T3-L1adipocyteswithIC50valuesof1.2and1.3μM,respectively[1].PIK-75(1-1000nM;5min)blocksthephosphorylationofPKBinducedbyinsulinonbothSer473andThr308inCHO-IRcellsinadose-dependentmanner,withanIC50of78nM[2].PIK-75(0.1-1000nM;48hours)inhibitstheproliferationandsurvivalofpancreaticcancercellsthrough1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEapoptoticcelldeath[3].PIK-75(0.1-1000nM)alsoreducesthecolonyformationofpancreaticcancerMIAPaCa-2andAsPC-1cells[3].CellViabilityAssay[3]CellLine:Humanpancreaticcancercells(MIAPaCa-2orAsPC-1)Concentration:0.1,0.3,1,3,10,30,100,300,and1000nMIncubationTime:48hoursResult:Submicromolarconcentrationwassufficienttoinhibittheproliferationofpancreaticcancer,MIAPaCa-2andAsPC-1cellsafter48-htreatment.WesternBlotAnalysis[2]CellLine:Overnight-starvedCHO-IRcellsConcentration:1,10,100,1000nMIncubationTime:5minutesResult:BlockedthephosphorylationofPKBinducedbyinsulin(1nM,10min)onbothSer473andThr308inadose-dependentmanner.PIK-75potentiatesanticanceractivityofGemcitabine(20mg/kg)invivo.Gemcitabine(20mg/kg)orPIK-75(2mg/kg)alonereducesthetumorgrowthtosimilardegree.BeneficialeffectofPIK-75/Gemcitabineisevidentasthiscombinationmarkedlyreducesthetumorgrowthinvivowithoutaffectingthebodyweightsofmice[3].体内研究PIK-75(2mg/kg)potentiatesanticanceractivityofGemcitabine(20mg/kg)invivo.Gemcitabine(20mg/kg)orPIK-75(2mg/kg)alonereducesthetumorgrowthtosimilardegree.BeneficialeffectofPIK-75/Gemcitabineisevidentasthiscombinationmarkedlyreducesthetumorgrowthinvivowithoutaffectingthebodyweightsofmice[3].AnimalModel:MicebearingtumorsofMIAPaCa-2[3]Dosage:2mg/kg;orcombinationwithGemcitabine(20mg/kg)Administration:Administeredinjection;5timesperweek.25daysResult:Reducedthetumorgrowthandenhancedtheantitumoreffect.户使⽤本产品发表的科研⽂献•ClinCancerRes.2020Apr15;26(8):2011-2021.•Molecules.2020Apr23;25(8):1980.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].KnightZA,etal.ApharmacologicalmapofthePI3-Kfamilydefinesaroleforp110alphaininsulinsignaling.Cell.2006May19;125(4):733-47.[2].ChaussadeC,etal.EvidenceforfunctionalredundancyofclassIAPI3Kisoformsininsulinsignalling.BiochemJ.2007Jun15;404(3):449-58.[3].DuongHQ,etal.InhibitionofNRF2byPIK-75augmentssensitivityofpancreaticcancercellstogemcitabine.IntJOncol.2014Mar;44(3):959-69.McePdfHeightCaution:Pro