ENMD-2076-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEENMD-2076Cat.No.:HY-10987ACASNo.:934353-76-1分⼦式:C₂₁H₂₅N₇分⼦量:375.47作⽤靶点:AuroraKinase;FLT3;VEGFR;FGFR;PDGFR;Src;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥31mg/mL(82.56mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6633mL13.3166mL26.6333mL5mM0.5327mL2.6633mL5.3267mL10mM0.2663mL1.3317mL2.6633mL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:≥2.5mg/mL(6.66mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(6.66mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.66mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性ENMD-2076多靶点激酶抑制剂，抑制AuroraA，Flt3，KDR/VEGFR2，Flt4/VEGFR3，FGFR1，FGFR2，Src，PDGFRα的IC50值分别为1.86，14，58.2，15.9，92.7，70.8，20.2and56.4nM。IC50&TargetAuroraAKDRFlt-4FGFR114nM(IC50)58.2nM(IC50)15.9nM(IC50)92.7nM(IC50)FGFR2PDGFRαFlt370.8nM(IC50)56.4nM(IC50)1.86nM(IC50)体外研究ENMD-2076isselectivetowardAuroraAversusAuroraB(IC50=350nM).ENMD-2076inhibitsHUVECgrowthwithanIC50valueof0.15mM.Against10humanleukemiacelllines,theIC50valuesrangefrom0.025to0.53mM.Withinthispanel,MV4:11cellsarethemostsensitivecellsbyafactorofgreaterthan4.Thelymphoma-derivedU937celllinetreatedwithENMD-2076showsthattheENMD-2076inducesadose-dependentincreaseinG2-M-phasearrestaswellastheinductionofapoptosis.ENMD-2076inhibitscellularFlt3ligand(FL)-inducedFlt3autophosphorylationinTHP-1cells,whichhavebeenshowntoexpressFL-responsivewild-typeFlt-3(18)withanIC50valueof28nM.ENMD-2076inhibitsstemcellfactor(SCF)-inducedKitautophosphorylationinMO7ecellswithanIC50valueof40nM.ENMD-2076inhibitsVEGFR2/KDRautophosphorylationwithanIC50valueof7nM[1].体内研究ENMD-2076treatmentresultsinstatisticallysignificant,dosedependentinhibitionoftumorgrowthortumorregression.Moreover,thereisnocorrelationbetweentumorgrowthrateandantitumorefficacy,whichwouldconceivablybeexpectedforamitotickinaseinhibitor,asfastgrowing(e.g.,A375melanoma)andslow-growing(e.g.,HT29coloncarcinoma)tumorsaresimilarlyinhibitedbyENMD-2076.ENMD-2076iswelltoleratedatdailydosesupto302mg/kg(equivalentto200mg/kgofthefreebase),withnoweightlossorsignsofmorbiditynotedinanystudyatthisdosewiththeexceptionoftheA375model[1].PROTOCOLKinaseAssay[1]RecombinantAuroraAandBkinaseenzymesassaysarecarriedoutinkinaseassaybuffer(50mMofHEPES,pH7.5,10mMofMgCl2,5mMofEGTA,0.05%Brij-35)supplementedwith2mMofDTT.ActivitiesaredeterminedatanATPconcentrationequivalenttotheapparentKmforeachenzyme,andanenzymeconcentrationthatresultsinapproximately30%phosphorylationofthepeptidesubstrateafter1hour.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEDose–responsecurvesofrelativeenzymeactivityversusENMD-2076concentrationareplottedwithGrafitandusedtocalculateIC50values[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]TheantiproliferativeeffectofENMD-2076onadherenttumorcelllinesismeasuredbyplating500cellsperwellina96-wellplateandincubatingwith9dosesofcompound,spanning0.3nMto125mM,for96hours.CellularproliferationismeasuredusingthesulforhodamineBassay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Celllinesareinjectedsubcutaneouslyorintothemammaryfatpad(MDA-MB-231only)of5-to6-Administration[1]week-oldCB.17SCIDorNCrnudemice.Tumorsareallowedtogrowfor10to50daysbeforedrugtreatment.AlltreatmentsarewithENMD-2076inwaterorENMD-2076freebaseinCMC-Tweenvehicle(0.075%carboxymethylcellulose,0.085%Tween80inwater),administeredorally.Percenttumorgrowthinhibitioniscalculated[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•AmJPathol.2019Oct;189(10):2090-2101.•IntJGynecolCancer.2017Oct;27(8):1666-1674.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].FletcherGC,etal.ENMD-2076isanorallyactivekinaseinhibitorwithantiangiogenicandantiproliferativemechanismsofaction.MolCancerTher.2011Jan;10(1):126-37.[2].WangX,etal.Preclinicalactivityofanovelmultipletyrosinekinaseandaurorakinaseinhibitor,ENMD-2076,agains