VX-984-M9831-DataSheet-生命科学试剂-MedChemExpressVIP

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVX-984Cat.No.:HY-19939SCASNo.:1476074-39-1Synonyms:M9831分⼦式:C₂₃H₂₁D₂N₇O分⼦量:415.49作⽤靶点:DNA-PK作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:10mg/mL(24.07mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4068mL12.0340mL24.0680mL5mM0.4814mL2.4068mL4.8136mL10mM0.2407mL1.2034mL2.4068mL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。-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：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥1mg/mL(2.41mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.41mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性VX-984(M9831)⼀种⼝服有效、选择性的、可透过⾎脑屏障的DNA-PK抑制剂。VX-984有效抑制NHEJ(⾮同性末端接合)，增加DSBs(DNA双链断裂)。VX-984可⽤于胶质母细胞瘤(GBM)和⾮⼩细胞肺癌(NSCLC)的研究。体外研究VX-984(0-500nM,30min)inhibitsradiation-inducedDNA-PKcsphosphorylationinU251andNSC11cells[1].VX-984(0-500nM)enhancestheradiosensitivityofU251andNSC11cellsinaconcentration-dependentmanner[1].VX-984inhibitstherepairofradiation-inducedDNAdouble-strandbreaks(DSBs)[1].VX-984(0-1μM)increasesalternatepathwaysofDSBrepair,includingHR(homologousrecombination)andmutagenicNHEJ(mNHEJ)[2].WesternBlotAnalysis[1]CellLine:U251andNSC11cellsConcentration:0,100,250,and500nMIncubationTime:30minResult:Showedaconcentration-dependentdecreaseinradiation-inducedDNA-PKcsphosphorylationineachgliomaline,whenVX-984wasdelivered1hourbeforeirradiation.VX-984treatmentalonehadnoeffect.体内研究VX-984(0-100mg/kg,Oralgavage,daily)inhibitsradiation-inducedDNA-PKcsphosphorylationinorthotopicbraintumorxenografts[1].VX-984(0-50mg/kg,Oralgavage,twiceadayfor2days)enhancestheradiosensitivityofbraintumorxenografts[1].AnimalModel:Athymicfemalenudemice(6-8weeksold,7-8mice/group,U251intracerebralxenografts)[1]Dosage:0,50,and100mg/kgAdministration:Oralgavage,daily,1or4hoursbeforeirradiation(10Gy)Result:ReducedthelevelsDNA-PKcsphosphorylationafterirradiation.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:Athymicfemalenudemice(6-8weeksold,7mice/group,U251intracerebralxenografts)[1]Dosage:0,50mg/kgAdministration:Oralgavage,twiceaday,30minutesbeforeand4hoursfollowinglocalirradiationofthetumor(3Gy)for3consecutivedays(3×3Gy)Result:VX-984treatmentofU251tumorsalonehadnosignificanteffectonoverallsurvivalascomparedwithvehicle;radiationaloneresultedinanincreaseinsurvival.VX-984andradiationcombinationprotocolincreasedtumorradiosensitivity,andsignificantlyincreasedthesurvivalofmicecomparedwithradiationalone.户使⽤本产品发表的科研⽂献•CellDeathDis.2020Jul30;11(7):602.•TranslOncol.2020Nov;13(11):100834.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TimmeCR,etal.TheDNA-PKInhibitorVX-984EnhancestheRadiosensitivityofGlioblastomaCellsGrownInVitroandasOrthotopicXenografts.MolCancerTher.2018Jun;17(6):1207-1216.[2].KhanAJ,etal.VX-984isaselectiveinhibitorofnon-homologousendjoining,withpossiblepreferentialactivityintransformedcells.Oncotarget.2018May25;9(40):25833-25841.[3].DianeBoucher,etal.Abstract3716:PotentradiationenhancementwithVX-984,aselectiveDNA-PKcsinhibitorforthetreatmentofNSCLC.CancerRes(2016)76(14_Supplement):3716.McePdfHeightCaut