Ribociclib-succinate-LEE011-succinate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERibociclibsuccinateCat.No.:HY-15777BCASNo.:1374639-75-4Synonyms:LEE011succinate分⼦式:C₂₇H₃₆N₈O₅分⼦量:552.63作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:41.67mg/mL(75.40mM;Needultrasonic)H2O:4.17mg/mL(7.55mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8095mL9.0476mL18.0953mL5mM0.3619mL1.8095mL3.6191mL10mM0.1810mL0.9048mL1.8095mL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(sealedstorage,awayfrommoisture)。-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:≥2.08mg/mL(3.76mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.76mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.76mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Ribociclibsuccinate(LEE011succinate)⼀种⾼度特异性的CDK4/6抑制剂，IC50值分别为10nM和39nM，对cyclinB/CDK1复合体的活性低于其1000倍。IC50&TargetCDK4CDK610nM(IC50)39nM(IC50)体外研究Treatingapanelof17neuroblastomacelllineswithRibociclib(LEE011)acrossafour-logdoserange(10to10,000nM).TreatmentwithRibociclibsignificantlyinhibitssubstrateadherentgrowthrelativetothecontrolin12ofthe17neuroblastomacelllinesexamined(meanIC50=306±68nM,consideringsensitivelinesonly,wheresensitivityisdefinedasanIC50oflessthan1μM.Ribociclibtreatmentoftwoneuroblastomacelllines(BE2CandIMR5)withdemonstratedsensitivitytoCDK4/6inhibitionresultsinadose-dependentaccumulationofcellsintheG0/G1phaseofthecellcycle.ThisG0/G1arrestbecomessignificantatRibociclibconcentrationsof100nM(p=0.007)and250nM(p=0.01),respectively[2].体内研究CB17immunodeficientmicebearingBE2C,NB-1643(MYCNamplified,sensitiveinvitro),orEBC1(non-amplified,resistantinvitro)xenograftsaretreatedoncedailyfor21dayswithRibociclib(LEE011;200mg/kg)orwithavehiclecontrol.Thisdosingstrategyiswelltolerated,asnoweightlossorothersignsoftoxicityareobservedinanyofthexenograftmodels.Tumorgrowthissignificantlydelayedthroughoutthe21daysoftreatmentinmiceharboringtheBE2Cor1643xenografts(both,p[2].PROTOCOLCellAssay[2]Cellsaregrownfor24hoursin35mmplates,treatedwith500nMRibociclibfor6days,andthenfixedandstainedovernight.CellsarethenimagedforSA-β-galusinganAxioObserverD.1phasecontrastmicroscope.ThepercentageofSA-β-galpositivecellsisdeterminedbycountingthenumberofpositivecellspresentinthreeseparatemicroscopeframes,andthennormalizingtothecontrol.Toassessapoptoticactivity,cellsareplatedintriplicatein96wellplates,treatedwithRibociclib,andassayedforcaspase3/7activation16hoursaftertreatmentwithCaspase-Glo3/7.CellstreatedwithSN-38areusedasapositivecontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]TheBE2C,NB-1643,orEBC1cellline-derivedxenograftsareimplantedsubcutaneouslyintotherightflankofCB17SCID-/-mice.Animalsbearingengraftedtumorsof200-600mm3arethenrandomizedtooral2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEtreatmentwith200mg/kgRibociclibin0.5%methylcellulose(n=10)orvehicle(n=10)dailyforatotalof21days.Tumorburdenisdeterminedperiodicallythroughouttreatmentaccordingtotheformula(π/6)×d2,wheredrepresentsthemeantumordiameterobtainedbycalipermeasurement.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•MolCell.2017Oct19;68(2):336-349.e6.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•NatCommun.2022Aug10;13(1):4689.•NatCommun.2021Sep10;12(1):5386.•NatCommun.2021Aug25;12(1):5112.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].VanArsdaleT,etal.MolecularPathways:TargetingtheCyclinD-CDK4/6AxisforCancerTreatment.ClinCancerRes.2015Jul1;21(13):2905-10.[2].RaderJ,etal.DualCDK4/CDK6InhibitionInducesCell-CycleArrestandSenescenceinNeuroblastoma.ClinCancerRe