Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBuparlisibCat.No.:HY-70063CASNo.:944396-07-0Synonyms:BKM120;NVP-BKM120分?式:C??H??F?N?O?分?量:410.39作?靶點(diǎn):PI3K;Apoptosis作?通路:PI3K/Akt/mTOR;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(243.67mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4367mL12.1835mL24.3671mL5mM0.4873mL2.4367mL4.8734mL10mM0.2437mL1.2184mL2.4367mL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。-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?；如在配制過程中出現(xiàn)沉淀1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE、析出現(xiàn)象，可以通過加熱和/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%salineSolubility:≥2.5mg/mL(6.09mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.09mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.09mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(6.09mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.09mM);Clearsolution6.請(qǐng)依序添加每種溶劑：50%PEG300>>50%salineSolubility:2.08mg/mL(5.07mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Buparlisib(BKM120;NVP-BKM120)?種pan-classIPI3K抑制劑，作?于p110α/p110β/p110δ/p110γ，IC50分別為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)體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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