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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERibociclibCat.No.:HY-15777CASNo.:1211441-98-3Synonyms:LEE011分⼦式:C₂₃H₃₀N₈O分⼦量:434.54作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:20mg/mL(46.03mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3013mL11.5064mL23.0128mL5mM0.4603mL2.3013mL4.6026mL10mM0.2301mL1.1506mL2.3013mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥0.89mg/mL(2.05mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥0.89mg/mL(2.05mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.89mg/mL(2.05mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥1mg/mL(2.30mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.30mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Ribociclib(LEE011)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[1]。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,treatedwith500nMRibociclib(LEE011)for6days,andthenfixedandstainedovernight.CellsarethenimagedforSA-β-galusinganAxioObserverD.1phasecontrastmicroscope.ThepercentageofSA-β-galpositivecellsisdeterminedbycountingthenumberofpositivecellspresentinthreeseparatemicroscopeframes,andthennormalizingtothecontrol.Toassessapoptoticactivity,cellsareplatedintriplicatein96wellplates,treatedwithRibociclib(LEE011),andassayedforcaspase3/7activation16hoursaftertreatmentwithCaspase-Glo3/7.CellstreatedwithSN-38areusedasapositivecontrol[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalMice[2]Administration[2]TheBE2C,NB-1643,orEBC1cellline-derivedxenograftsareimplantedsubcutaneouslyintotherightflankofCB17SCID-/-mice.Animalsbearingengraftedtumorsof200-600mm3arethenrandomizedtooraltreatmentwith200mg/kgRibociclib(LEE011)in0.5%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.ClinCancerR