BI-882370-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBI-882370Cat.No.:HY-107779CASNo.:1392429-79-6分?式:C??H??F?N?O?S分?量:569.67作?靶點:Raf作?通路:MAPK/ERKPathway儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:5mg/mL(8.78mM;ultrasonicandwarmingandheatto60°C)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7554mL8.7770mL17.5540mL5mM0.3511mL1.7554mL3.5108mL10mM---------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BI-882370?種?效選擇性的RAF激酶抑制劑，其結(jié)合位于BRAF激酶的DFG-out?活性構(gòu)象處(ATP結(jié)合位點)。BI-882370抑制BRAFV600E-mutant,WTBRAF和CRAF激酶的IC50值分別為0.4，0.8和0.6nM。BI-882370也可以抑制SRC家族激酶。1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIC50&TargetBrafc-RafBRafV600E0.6nM(IC50)0.8nM(IC50)0.4nM(IC50)體外研究BI-882370(0.9-6000nM;3days)inhibitstheBRAF-mutanthumanmelanomaandcolorectalcancercellsproliferationwithaEC50rangeof1-10nM[1].BI882370(0.1-100nM,0.1-3000nM;2hours)resultsinareductionofp-MEK1/2,p-ERK1/2andcyclinD1/D2expressioninBRAFV600E-mutantA375cells;inducesphosphorylationofMEK1/2andenhancedphosphorylationofERK1/2inWTBROcells(3-300nM)[1].BI882370(0.1-100nM,0.1-3000nM;24hours)suppressescyclinD1/D2expression,inducesKip1/p27expressionatconcentrationsof1nMorhigherinBRAFV600E-mutantA375cells,expressionofcyclinsD1/D2orKip1/p27isnotaffectedinWTBROcells[1].CellProliferationAssay[1]CellLine:BRAF-mutantandWTmelanomacelllines(A101D,A375,SK-MEL-28,G-361,andBRO);Colorectalcancercelllines(COLO205,HT-29,LS411N,andHCT-116)Concentration:0.9-6000nMIncubationTime:3daysResult:ShowedaEC50rangeof1-10nMinanextendedpanelofBRAF-mutanthumanmelanomaandcolorectalcancercell;whileproliferationofBRAFWTcellswasinhibitedwithEC50>1μM.WesternBlotAnalysis[1]CellLine:BRAFV600E-mutantA375cells;BRAFWT,NRAS-mutantBRO(WTBRO)cellsConcentration:0.1-100nM;0.1-3000nMIncubationTime:2hours;24hoursResult:Resultedinareductionofphospho-MEK1/2signalsandcyclinD1/D2expressioninBRAFV600E-mutantA375cells.體內(nèi)研究BI-882370(deliverorally;25mg/kg,50mg/kg;twicedaily;2weeks)isefficaciousinmultiplemousemodelsofBRAF-mutantmelanomasandcolorectalcarcinomas,showssuperiorefficacycomparedwithVemurafenib,Dabrafenib,orTrametinib[1].BI-882370(deliverorally;25mg/kg;twicedaily;40days)developesresistancewithin3weeks,butresistanceisnotobservedduring5weeksofsecond-linetherapyincombinationwithtrametinib[1].BI-882370(deliverorally;60mg/kg;oncedaily;2weeks)indicateslackoftoxicityintermsofclinicalchemistry,hematology,pathology,andtoxicogenomicsinrats[1].AnimalModel:HumanmelanomaxenograftsinnudemicewithBRAF-mutantmelanomasandcolorectalcarcinomascells(A375,COLO205;G-361,HT-29cells)[1]Dosage:25mg/kg;50mg/kg2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:Deliverorally;25mg/kg,50mg/kg;twicedaily;2weeksResult:Regressedtumorspartially,upondiscontinuation,tumorregrowthwasmarkedlydelayed.REFERENCES[1].WaizeneggerIC,etal.ANovelRAFKinaseInhibitorwithDFG-Out-BindingMode:HighEfficacyinBRAF-MutantTumorXenograftModelsintheAbsenceofNormalTissueHyperproliferation.MolCancerTher.2016Mar;15(3):354-65.McePdfHeightCaution:Producthas