Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEFLT3-IN-15Cat.No.:HY-146886CASNo.:2435562-99-3分?式:C??H??ClFN?O?分?量:443.9作?靶點(diǎn):FLT3作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性FLT3-IN-15?種有效且具有?服活性的FLT3抑制劑，對(duì)FLT3和FLT3/D835Y的IC50分別為0.87nM和0.32nM。FLT3-IN-15可?于研究急性髓系??病[1]。IC50&TargetIC50:0.87nM(FLT3),0.32nM(FLT3/D835Y)[1]體外研究FLT3-IN-15(compound36)(0-100nM)exhibitsanti-proliferativeactivitiesagainstMOLM14celllines[1].FLT3-IN-15(0-1μM;72hours)showsextremelymoresensitiveagainstMV4-11cellsthanK562cellline,anddisplayedgoodsafetyprofilesagainstothercancercelllines[1].FLT3-IN-15(0.01-1μM;4hours)showsstronglyblockageofthephosphorylationofSTAT5andErk1/2inMV4-11cells[1].CellProliferationAssayCellLine:MOLM14wildtypecells,MOLM14-ITDcells,MOLM14-ITD-D835Ycells,MOLM14-ITD-F691Lcells[1]Concentration:0-100nMIncubationTime:Result:Exhibitedanti-proliferativeactivitiesagainstMOLM14celllines,withGI50sof4.88±0.67nM,1.85±0.06nM,1.87±0.36nMand3.27±0.99nMinMOLM14wildtypecells,MOLM14-ITDcells,MOLM14-ITD-D835YcellsandMOLM14-ITD-F691Lcells,respectively.1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellProliferationAssayCellLine:MV4-11,K562,A549,HepG2,MDA-MB-231,HCT-116,PC3andSK-OV-3[1]Concentration:0-1μMIncubationTime:72hoursResult:ShowedextremelymoresensitiveagainstMV4-11cells(GI50=1nM)thanK562cellline,anddisplayedgoodsafetyprofilesagainstothercancercelllines.WesternBlotAnalysisCellLine:MV4-11[1]Concentration:10nM,100nMand1μMIncubationTime:4hoursResult:ShowedstronglyblockageofthephosphorylationofSTAT5andErk1/2.體內(nèi)研究FLT3-IN-15(20mg/kg;PO;daily,for21days)resultsintherapidandcompleteremissionoftumorsinallmice[1].FLT3-IN-15(2000mg/kg;PO;single)causesonefemalemousediedatday6,andtheLD50valueiscalculatedas4,950mg/kginfemalemice[1].FLT3-IN-15(10μM)shows21.4%inhibitionofhERGligandbinding[1].FLT3-IN-15(10mg/kg;POandIV;single)exhibitsanAUClastof25.0μg·min/mL,aCmaxof36.5ng/mL,andaremarkableincreaseintheoralbioavailabilityof42.6%[1].PharmacokineticParametersofFLT3-IN-15inmaleICRmice[1].PO(10mg/kg)IV(10mg/kg)AUClast(μg·min/mL)25.0±11.658.5±57.4AUCinf(μg·min/mL)62.1±58.6103.4±95.3MRT(hr)2811.3±2713.01257.1±1084.1T1/2(hr)1775.7±1901.01099.2±945.8CL(mL/min/kg)158.7±98.7VSS(L/kg)127891±104764Cmax(ng/mL)36.5±24.3Tmax(min)390.0±366.0Xu,24h(%)0.001±0.00.002±0.002GI24h(%)0.05±0.050.24±0.02F(%)42.9AnimalModel:BALB/cnu/nu(injectedwithMV4-11)[1]Dosage:20mg/kgAdministration:PO;daily,for21daysResult:Resultedintherapidandcompleteremissionoftumorsinallmice,andnoweightlossoranyothersignsoftoxicityduringtheadministrationperiod.AnimalModel:FemaleICRmice[1]Dosage:2000mg/kg2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:PO;singleResult:Causedonefemalemouseofthe2,000mg/kggroupdiedatday6andtheapproximatelethaldose(ALD)isdeterminedover2,000mg/kginmalemiceand2,000mg/kginfemalemice,respectively;theLD50valuewascalculatedas4,950mg/kginfemalemice.AnimalModel:MaleICRmice[1]Dosage:10mg/kgAdministration:POandIV;single(PharmacokineticsAnalysis)Result:ExhibitedanAUClastof25.0μg·min/mL,aCmaxof36.5ng/mL,andaremarkableincreaseintheoralbioavailabilityof42.6%.REFERENCES[1].JeongP,MoonY,LeeJH,etal.Discoveryoforallyactiveindirubin-3'-oximederivativesaspotenttype1FLT3inhibitorsforacutemyeloidleukemia.EurJMedChem.2020;195:112205.McePdfHeightCauti