BMS-906024-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBMS-906024Cat.No.:HY-15670CASNo.:1401066-79-2分⼦式:C₂₆H₂₆F₆N₄O₃分⼦量:556.5作⽤靶点:γ-secretase;Notch作⽤通路:NeuronalSignaling;StemCell/Wnt储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:260mg/mL(467.21mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7969mL8.9847mL17.9695mL5mM0.3594mL1.7969mL3.5939mL10mM0.1797mL0.8985mL1.7969mL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。BIOLOGICALACTIVITY⽣物活性BMS-906024⼀种⼝服有效，选择性的γ分泌酶(γ-secretase;gammasecretase)抑制剂。BMS-906024Notch受体抑制剂，对Notch1，-2，-3和-4受体的IC50值分别为1.6nM，0.7nM，3.4nM和2.9nM。BMS-906024表现⼴谱抗肿瘤活性。IC50&TargetIC50:1.6nM(Notch1),0.7nM(Notch2),3.4nM(Notch3)and2.9nM(Notch4)[2]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体外研究BMS-906024(5-100nM;72hours)reducesNotch1ICDlevelsinallsixlungcancercelllines.BMS-906024at100nM,hasnoeffectontotalNotch1,anddown-regulatedHes1transcript[1].Incancercellproliferationassays,BMS-906024inhibitsbothleukemia(TALL-1)andtriple-negativebreastcancer(MDA-MB-468)cellswithIC50of-4nM[2].BMS-906024(100nM;for72hours)enhancestheanti-tumoractivityofPaclitaxelinvitro[1].WesternBlotAnalysis[1]CellLine:NSCLCcelllines(A549,H358,H1975,H2444,H1792,HCC44)Concentration:5,10,25,50,100nMIncubationTime:72hoursResult:ReducedNotch1ICDlevelsinallsixlungcancercelllinestestedatconcentrationsaslowas5nM,withmaximaldepletionat50-100nM.体内研究BMS-906024(8.5mg/kg;oralgavage;days1through4ofeachweekfor3weeks)significantlyenhancesthetumorgrowthinhibitionofPaclitaxel(36mg/kg).BMS-906024enhancesPaclitaxel-mediatedcytotoxicityinvivoinNSCLCthroughacombinationofinhibitingproliferationandpromotingapoptosis,inap21andp57-independentmanner[1].BMS-906024hasaT1/2of4.6/5.3hours,aCmaxof1/0.3μMandanAUCof3.4/1.9μM•hourforIV/PO[2].AnimalModel:Sixto12-week-oldfemaleNODscidgamma(NSG)micewithKRAS-andBRAF-WTPDX-T42xenografts[1]Dosage:8.5mg/kgAdministration:oralgavage;days1through4ofeachweekfor3weeksResult:SignificantlyenhancedthetumorgrowthinhibitionofPaclitaxel(36mg/kg),buthadnosignificanteffectonCisplatin(2mg/kg)treatment.AnimalModel:Mouse[2]Dosage:1mg/kg(PharmacokineticAnalysis)Administration:IVorPOResult:HadaT1/2of4.6/5.3hours,aCmaxof1/0.3μMandanAUCof3.4/1.9μM•hourforIV/PO.户使⽤本产品发表的科研⽂献•ResearchSquarePreprint.2020Nov.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].MorganKM,etal.GammaSecretaseInhibitionbyBMS-906024EnhancesEfficacyofPaclitaxelinLungAdenocarcinoma.MolCancerTher.2017Dec;16(12):2759-2769.[2].GavaiAV,etal.DiscoveryofClinicalCandidateBMS-906024:APotentPan-NotchInhibitorfortheTreatmentofLeukemiaandSolidTumors.ACSMedChemLett.2015Mar11;6(5):523-7.McePdfHeightCaution:Producthasnotbeenfullyva