Ribociclib-succinate-LEE011-succinate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERibociclibsuccinateCat.No.:HY-15777BCASNo.:1374639-75-4Synonyms:LEE011succinate分?式:C??H??N?O?分?量:552.63作?靶點(diǎn):CDK作?通路:CellCycle/DNADamage儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:41.67mg/mL(75.40mM;Needultrasonic)H2O:4.17mg/mL(7.55mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8095mL9.0476mL18.0953mL5mM0.3619mL1.8095mL3.6191mL10mM0.1810mL0.9048mL1.8095mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.76mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.76mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.76mM);ClearsolutionBIOLOGICALACTIVITY?物活性Ribociclibsuccinate(LEE011succinate)?種?度特異性的CDK4/6抑制劑，IC50值分別為10nM和39nM，對(duì)cyclinB/CDK1復(fù)合體的活性低于其1000倍。IC50&TargetCDK4CDK610nM(IC50)39nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEtreatmentwith200mg/kgRibociclibin0.5%methylcellulose(n=10)orvehicle(n=10)dailyforatotalof21days.Tumorburdenisdeterminedperiodicallythroughouttreatmentaccordingtotheformula(π/6)×d2,wheredrepresentsthemeantumordiameterobtainedbycalipermeasurement.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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