BMS-906024-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBMS-906024Cat.No.:HY-15670CASNo.:1401066-79-2分?式:C??H??F?N?O?分?量:556.5作?靶點:γ-secretase;Notch作?通路:NeuronalSignaling;StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:260mg/mL(467.21mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7969mL8.9847mL17.9695mL5mM0.3594mL1.7969mL3.5939mL10mM0.1797mL0.8985mL1.7969mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。BIOLOGICALACTIVITY?物活性BMS-906024?種?服有效，選擇性的γ分泌酶(γ-secretase;gammasecretase)抑制劑。BMS-906024Notch受體抑制劑，對Notch1，-2，-3和-4受體的IC50值分別為1.6nM，0.7nM，3.4nM和2.9nM。BMS-906024表現(xiàn)?譜抗腫瘤活性。IC50&TargetIC50:1.6nM(Notch1),0.7nM(Notch2),3.4nM(Notch3)and2.9nM(Notch4)[2]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE體外研究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.體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻?ResearchSquarePreprint.2020Nov.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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