ZM-447439-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZM-447439Cat.No.:HY-10128CASNo.:331771-20-1分⼦式:C₂₉H₃₁N₅O₄分⼦量:513.59作⽤靶点:AuroraKinase;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(48.68mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9471mL9.7354mL19.4708mL5mM0.3894mL1.9471mL3.8942mL10mM0.1947mL0.9735mL1.9471mL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%salineSolubility:≥2.5mg/mL(4.87mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.87mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性ZM-447439极光激酶(aurora)抑制剂，对auroraA和B的IC50值分别为110和130nM。IC50&TargetAuroraAAuroraB110nM(IC50)130nM(IC50)体外研究CellstreatedwithZM-447439progressthroughinterphase,entermitosisnormally,andassemblebipolarspindles.However,chromosomealignment,segregation,andcytokinesisallfail.ZM-447439inhibitscelldivisionandinhibitmitoticphosphorylationofhistoneH3.ZM-447439preventschromosomealignmentandsegregation.ZM-447439compromisesspindlecheckpointfunction.ZM-447439inhibitskinetochorelocalizationofBubR1,Mad2,andCenp-E[1].InhibitionofAurorakinasebyZM-447439reduceshistoneH3phosphorylationatSer10inHep2carcinomacells.MultipolarspindlesareinducedintheseZM-treatedG2/M-arrestedcellswithaccumulationof4N/8NDNA,similartocellswithgeneticallysuppressedAurora-B.ZM-447439treatmentinducescellapoptosis.ZM-447439inhibitionofAurorakinaseispotentlyinassociationwithdecreaseofAktphosphorylationatSer473anditssubstratesGSK3α/βphosphorylationatSer21andSer9[2].PROTOCOLKinaseAssay[1]1ngpurifiedrecombinantenzymeisaddedtoareactioncocktailcontainingbuffer,10μMpeptidesubstrate,10μMforAuroraAor5μMATPforAuroraB,and0.2μCiγ[33P]ATP,andisthenincubatedatroomtemperaturefor60min.Reactionsarestoppedbyadditionof20%phosphoricacid,andtheproductsarecapturedonP30nitrocellulosefiltersandassayedforincorporationof33PwithaBetaplatecounter.NoenzymeandnocompoundcontrolvaluesareusedtodeterminetheconcentrationofZM-447439,whichgave50%inhibitionofenzymeactivity[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]Todeterminecloningefficiency,MCF7cellsareplatedinphenolredfreeDMEplus5%strippedserum,andarethentreatedwithorwithouttheanti-estrogenICI182780at1μMfor48h.ZM-447439isthenaddedattheindicatedconcentrationsfor72h.Thecellsareharvested,washed,and-400cellsplatedineachwellofa6-wellplateincompletemediawithoutZM-447439.After10d,thecoloniesarefixed,stainedwithcrystalviolet,andcounted.ThecloningefficiencyrepresentsthenumberofcoloniesonZM-447439-treatedplatescomparedwithDMSO-treatedcontrols[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•EBioMedicine.2021Aug5;70:103510.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•Elife.2020Dec7;9:e61405.•bioRxiv.2021Feb5.•HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].DitchfieldC,etal.AuroraBcoupleschromosomealignmentwithanaphasebytargetingBubR1,Mad2,andCenp-Etokinetochores.JCellBiol.2003Apr28;161(2):267-80.[2].LongZJ,etal.ZM447439inhibitionofaurorakinaseinducesHep2cancercellapoptosisinthree-dimensionalculture.CellCycle.2008May15;7(10):1473-9.MceP