Venetoclax-ABT-199-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVenetoclaxCat.No.:HY-15531CASNo.:1257044-40-8Synonyms:ABT-199;GDC-0199分⼦式:C₄₅H₅₀ClN₇O₇S分⼦量:868.44作⽤靶点:Bcl-2Family;Autophagy作⽤通路:Apoptosis;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:77.5mg/mL(89.24mM;Needultrasonic)Ethanol:<1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.1515mL5.7575mL11.5149mL5mM0.2303mL1.1515mL2.3030mL10mM0.1151mL0.5757mL1.1515mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.58mg/mL(2.97mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(2.88mM);Suspendedsolution;Needultrasonicandwarming3.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥5.25mg/mL(6.05mM);Clearsolution4.请依序添加每种溶剂：60%phosal50propyleneglycol(PG),30%polyethyleneglycol400(PEG400),10%ethanolSolubility:20mg/mL(23.03mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Venetoclax(ABT-199;GDC-0199)⼀种⾼效，有选择性和⼝服有效的Bcl-2抑制剂，Ki⼩于0.01nM。Venetoclax可以诱导⾃噬(autophagy)作⽤。IC50&TargetBcl-2Bcl-xLBcl-W0.01nM(Ki)48nM(Ki)245nM(Ki)体外研究Venetoclax(ABT-199)potentlykillsFL5.12-BCL-2cells(EC50=4nM),Venetoclax(ABT-199)showsmuchweakeractivityagainstFL5.12-BCL-XLcells(EC50=261nM).ABT-199alsoshowsselectivityincellularmammaliantwo-hybridassays,whereitdisruptsBCL-2-BIMcomplexes(EC50=3nM)butismuchlesseffectiveagainstBCL-XL-BCL-XS(EC50=2.2μM)orMCL-1-NOXAcomplexes[1].体内研究Afterasingleoraldoseof12.5mgperkgbodyweightinxenograftsderivedfromRS4;11cells(ALL),Venetoclax(ABT-199)causesamaximaltumorgrowthinhibition(TGImax)of47%(P[1].Treatmentofestablishedxenografted(amousexenograftmodeloftheT-ALLcelllineLOUCY)tumorswithVenetoclax(ABT-199)100mg/kgfor4daysresultsinasignificantreductionofleukemicburden[2].PROTOCOLCellAssay[1]RS4;11cellsareseededat50,000perwellin96-wellplatesandtreatedwithcompoundsdilutedinhalf-logstepsstartingat1μMandendingat0.00005μM.Allotherleukemiaandlymphomacelllinesareseededat15,000-20,000cellsperwellintheappropriatemediumandincubatedwithVenetoclaxorNavitoclaxfor48h.EffectsonproliferationaredeterminedusingCellTiterGloreagent.EC50valuesaredeterminedbynonlinearregressionanalysisoftheconcentration-responsedata.MouseFL5.12-BCL-2andFL5.12-BCL-XLcellsarepropagatedandassessed.Bak-/-Bax-/-doubleknockoutmouseembryonicfibroblastsareseededinto96-wellmicrotiterplatesat5,000cellsperwellinDMEMsupplementedwith10%FBS.Venetoclax(ABT-199)inthesameculturemediumisaddedinhalf-logdilutionsstartingat5μM.Thecellsarethenincubatedat37°C(5%CO2)for48h,andtheeffectsonproliferationaredeterminedusingCellTiterGloreagent[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAdministration[2]Nonobesediabetic/severecombinedimmunodeficientγ(NSG)miceareinjectedat6weeksofageinthetailveinwith150µLphosphate-bufferedsalinecontaining5×106luciferase-labeledLOUCYcells.Atregulartimepoints,thebioluminescenceismeasuredusingtheIVISLuminaIIimagingsystem.At6weeks,thecellsareengraftedandthemicearerandomlydividedinto2groups(withanequalnumberofmalesandfemalesinbothgroups),andthetreatmentisstartedonday0.MicearetreatedwithVenetoclax(ABT-199)100mg/kgbodyweightorwithvehicleviaoralgavagefor4consecutivedays.Atdays0,2,and4thebioluminesceneismeasured.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Nature.2021Mar;591(7850):477-481.•Cell.2022Apr28;185(9):1521-1538.e18.•CancerCell.2020Dec14;38(6):872-890.e6.•CancerCell.2018Aug13;34(2):271-285.e7.•CancerCell.2017Oct9;32(4):490-505.e10.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SouersAJ,etal.ABT-199,apotentandselectiveBCL-2inhibitor,achievesantitumoractivitywhilesparingplatelets.NatMed.2013Feb;19(2):202-8.[2].PeirsS,etal.ABT-199mediatedinhibitionofBCL-2asanoveltherapeuticstrategyinT-cellacutelymphoblasticleukemia.Blood.2014Dec11;124(25):3738-47.[3].BiC,etal.Inhibitionof4EBPphosphorylationmediatesthecytotoxiceffectofmechanistictargetofrapamycinkinaseinhibitorsinaggressiveB-celllymp