VX-984-M9831-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVX-984Cat.No.:HY-19939SCASNo.:1476074-39-1Synonyms:M9831分?式:C??H??D?N?O分?量:415.49作?靶點(diǎn):DNA-PK作?通路:CellCycle/DNADamage;PI3K/Akt/mTOR儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:10mg/mL(24.07mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4068mL12.0340mL24.0680mL5mM0.4814mL2.4068mL4.8136mL10mM0.2407mL1.2034mL2.4068mL請(qǐng)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儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥1mg/mL(2.41mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.41mM);ClearsolutionBIOLOGICALACTIVITY?物活性VX-984(M9831)?種?服有效、選擇性的、可透過(guò)?腦屏障的DNA-PK抑制劑。VX-984有效抑制NHEJ(?同性末端接合)，增加DSBs(DNA雙鏈斷裂)。VX-984可?于膠質(zhì)母細(xì)胞瘤(GBM)和??細(xì)胞肺癌(NSCLC)的研究。體外研究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.體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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