Abemaciclib-methanesulfonate-LY2835219-methanesulfonate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAbemaciclibmethanesulfonateCat.No.:HY-16297CASNo.:1231930-82-7Synonyms:LY2835219methanesulfonate分⼦式:C₂₈H₃₆F₂N₈O₃S分⼦量:602.7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H2O:125mg/mL(207.40mM;Needultrasonic)DMSO:10mg/mL(16.59mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6592mL8.2960mL16.5920mL5mM0.3318mL1.6592mL3.3184mL10mM0.1659mL0.8296mL1.6592mL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：0.5%HEC1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:12.5mg/mL(20.74mM);Clearsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.15mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(4.15mM);Suspendedsolution;Needultrasonic4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.15mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2mg/mL(3.32mM);Suspendedsolution;Needultrasonic6.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2mg/mL(3.32mM);Clearsolution7.请依序添加每种溶剂：PBSSolubility:25mg/mL(41.48mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Abemaciclibmethanesulfonate(LY2835219methanesulfonate)选择性的CDK4/6抑制剂，抑制CDK4/CDK6的IC50分别为2nM和10nM。IC50&TargetCdk4/cyclinD1CDK6/cyclinD1CDK2/cyclinECDK9/cyclinT12nM(IC50)10nM(IC50)504nM(IC50)57nM(IC50)CDK1/cyclinB1CDK7/Mat1/cyclinH1Cdk5/p25CDK5/p351627nM(IC50)3910nM(IC50)355nM(IC50)287nM(IC50)PIM1PIM2HIPK2DYRK250nM(IC50)3400nM(IC50)31nM(IC50)61nM(IC50)CK2GSK3bJNK3FLT3(D835Y)117nM(IC50)192nM(IC50)389nM(IC50)403nM(IC50)FLT3DRAK13960nM(IC50)659nM(IC50)体外研究Abemaciclib(LY2835219)reducescellviabilitywiththeIC50valuesrangingfrom0.5μMto0.7μM,inhibitsAktandERKsignalingbutnotmTORactivationatheadandnecksquamouscellcarcinoma(HNSCC)cells[1].Abemaciclib(LY2835219)showsinhibitiononA375R1-4,M14R,andSH4RwithEC50valuesrangingfrom0.3to0.6μM;AbemaciclibinhibitstheproliferationoftheparentalA375andresistantA375RV1andA375RV2cellswithsimilarpotencieswithIC50valuesof395,260,and463nM,respectively[2].Abemaciclib(LY2835219)inhibitsCDK4andCDK6withlownanomolarpotency,inhibitsRbphosphorylationresultinginaG1arrestandinhibitionofproliferation,anditsactivityisspecificforRb-proficientcells[3].体内研究Abemaciclib(LY2835219)(45mg/kg,p.o.)incombinationwithRAD001causesacooperativeantitumor2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEeffectinHNSCCxenografttumor[1].Abemaciclib(LY2835219)(45or90mg/kg,p.o.)showssignificanttumorgrowthinhibitioninanA375xenograftmodel[2].PROTOCOLCellAssay[1]Cellsareseededina96-wellplate,allowedtoadhereovernight,andtreatedwithDMSOcontrol(0.1%v/v)ortheindicatedcompoundsfor72h.CellviabilityandproliferationaredeterminedusingaCellCountingKitaccordingtothemanufacturer'sinstructions.TheinteractionbetweenAbemaciclib(LY2835219)andmTORinhibitorisdeterminedusingCompuSyn.Combinationindex(CI)valuesof1indicatesandadditivedruginteraction,whereasaCIof<1issynergisticandaCIof>1isantagonistic.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalSix-week-oldBALB/cfemalenudemiceareinjectedsubcutaneouslywithOSC-19(1×106)cells.WhentumorAdministration[1]sizesreachapproximately100mm3,micearerandomizedbytumorsizeandsubjectedtoeachtreatment.Atleast5micepertreatmentgroupareincluded.Eachgroupofmiceisdosedviadailyoralgavagewithvehicle,Abemaciclib(LY2835219)(45mg/kg/dor90mg/kg/d),RAD001(5mg/kg/d),oracombinationofboth.TheAbemaciclib(LY2835219)isdissolvedin1%HECin20mMphosphatebuffer(pH2.0).Tumorsizeandbodyweightaremeasuredtwiceweekly.Tumorvolumesarecalculatedusingthefollowingformula:V=(L×W2)/2(L,Length;W,width).Micearegavagedafinaltimeonday14andsacrificedthefollowingday.ThetumorsareremovedforWesternblotandimmunohistochemistry.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Nature.2017Aug24;548(7668):471-475.•Cell.2018Nov1;175(4):984-997.e24.•AdvFunctMater.2021Apr30.•NatMetab.2020Jan;2(1):41-49.•MolCell.2017Oct19;68(2):336-349.e6.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].KuBM,etal.TheCDK4/6inhibitorLY2835219haspotentactivityincombinationwithmTORinhibitorinheadandnecksquamouscellcarcinoma.Oncotarget.2016Mar22;7(12):14803-13.[2].YadavV,etal.TheCDK4/6inhibitorLY2835219overcomesPLX4032resistanceresultingfromMAPKreactivationandcyclinD1upregulation.MolCancerTher.2014Oct;13(10):2253-63.[3].GelbertLM,etal.PreclinicalcharacterizationoftheCDK4/6inhibitorL