Buparlisib-BKM120-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBuparlisibCat.No.:HY-70063CASNo.:944396-07-0Synonyms:BKM120;NVP-BKM120分⼦式:C₁₈H₂₁F₃N₆O₂分⼦量:410.39作⽤靶点:PI3K;Apoptosis作⽤通路:PI3K/Akt/mTOR;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(243.67mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4367mL12.1835mL24.3671mL5mM0.4873mL2.4367mL4.8734mL10mM0.2437mL1.2184mL2.4367mL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1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE、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%salineSolubility:≥2.5mg/mL(6.09mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.09mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.09mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(6.09mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.09mM);Clearsolution6.请依序添加每种溶剂：50%PEG300>>50%salineSolubility:2.08mg/mL(5.07mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Buparlisib(BKM120;NVP-BKM120)⼀种pan-classIPI3K抑制剂，作⽤于p110α/p110β/p110δ/p110γ，IC50分别为52nM/166nM/116nM/262nM。IC50&Targetp110αp110βp110δp110γ52nM(IC50)166nM(IC50)116nM(IC50)262nM(IC50)Vps34p110α-H1047Rp110α-E545KmTOR2.4μM(IC50)58nM(IC50)99nM(IC50)4.6μM(IC50)体外研究Buparlisib(NVP-BKM120)exhibits50-300nMactivityforclassIPI3K’s,includingthemostcommonp110αmutants.Additionally,NVP-BKM120exhibitslowerpotencyagainstclassIIIandclassIVPI3K's,where2,5,>5,and>25μMbiochemicalactivityisobservedforinhibitionofVPS34,mTOR,DNAPK,andPI4K,respectively[1].Buparlisib(NVP-BKM120)inducesmultiplemyeloma(MM)cellapoptosisinbothdose-andtime-dependentmanners.Buparlisib(NVP-BKM120)atconcentrations≥10μMinducessignificantapoptosisinalltestedMMcelllinesat24h(P50variesamongtestedMMcells.At24htreatment,IC50forARP-1,ARK,andMM.1Risbetween1and10μM,whileIC50forMM.1Sis50forU266isbetween10and100μM.Insummary,NVP-BKM120treatmentresultsinMMcellgrowthinhibitionandapoptosisindose-andtime-dependentmanners[2].体内研究InA2780xenografttumors,oraldosingofBuparlisib(NVP-BKM120)at3,10,30,60,and100mg/kgresultsinadosedependentmodulationofpAKTSer473.PartialinhibitionofpAKTSer473isobservedat3and10mg/kg,andnearcompleteinhibitionisobservedatdosesof30,60,or100mg/kg,respectively.InhibitionofpAKT(normalizedtototalAKT)trackedwellwithbothplasmaandtumordrugexposure[1].MicereceivingBuparlisib(NVP-BKM120)(5μMperkgperdayfor15days)treatmenthassignificantlysmallertumorburdensascomparewithcontrolmice,whicharemeasuredastumorvolume(P[2].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEPROTOCOLCellAssay[1]A2780cellsareculturedinDMEMsupplementedwith10%FBS.L-glutamine,sodiumpyruvate,andantibiotics.Cellsareplatedinthesamemediumatadensityof1000cellsperwell,100uLperwellintoblack-walled-clear-bottomplatesandincubatedfor3-5hours.Buparlisib(NVP-BKM120)suppliedinDMSO(20mM)aredilutedfurtherintoDMSO(7.5uLof20mMBuparlisib(NVP-BKM120)in22.5uLDMSO.Mixwell,transfer10uLto20uLDMSO,repeatuntil9concentrationshavebeenmade).ThedilutedBuparlisib(NVP-BKM120)solution(2uL),isthenaddedtocellmedium(500uL)cellmedium.Equalvolumesofthissolution(100uL)areaddedtothecellsin96wellplatesandincubatedat37ºCfor3daysanddevelopedusingCellTiterGlo.InhibitionofcellproliferationisdeterminedbyluminescencereadusingTrilux[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Six-toeight-week-oldfemaleseverecombinedimmunodeficiency(SCID)miceareused.SCIDmicearesubcutaneouslyinoculatedintherightflankwith1millionARP-1orMM.1Scellssuspendedin50μLphosphate-bufferedsaline(PBS).Afterpalpabletumordeveloped(tumordiameter≥5mm),micearetreatedwithintraperitonealinjectionofDMSO/PBSorBuparlisib(NVP-BKM120)(5μMperkgperday)for15days.Tumorsizesaremeasuredevery5days,andbloodsamplesarecollectedatthesameperiod.Tumorburdensareevaluatedbymeasuringtumorsizeanddetectingcirculatinghumankappachainorlambdachain.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatMed.2016Jul;22(7):723-6.•Nature.2022Nov30.•Nature.2018Aug;560(7719):499-503.•CancerDiscov.2020Aug;10(8):1226-1239.•CancerDiscov.2019Sep;9(9):1306-1323.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BurgerMT,etal.IdentificationofNVP-BKM120asaPotent,Selective,OrallyBioavailableClassIPI3KinaseInhibitorforTreatingCancer.ACSMedChemLett.2011Aug26;2(10):774-9.[2].ZhengY,etal.Novelphosphatidylinositol3-kinaseinhibitorNVP-BKM120inducesapoptosisinmyelomacellsandshowssynergisticanti-myelomaactivity.JMolMed(Berl).2012Jun;90(6):695-706.[3].NiJ,etal.Combin