PF15-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPF15Cat.No.:HY-143286分?式:C??H??N??O?分?量:855.94作?靶點(diǎn):PROTACs;FLT3作?通路:PROTAC;ProteinTyrosineKinase/RTK儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性PF15由FLT3kinase配體和CRBN配體相連的PROTAC，?種具有?選擇性的FLT3-ITD降解劑，其DC50值為76.7nM。PF15能顯著抑制FLT3-ITD陽(yáng)性細(xì)胞的增殖，下調(diào)FLT3和STAT5的磷酸化。PF15還能抑制??模型中腫瘤的?長(zhǎng)，可?于??病的研究。體外研究PF15(0-1000nM;72h)showsgoodanti-proliferationactivityinMV4-11,Molm-13andBaF3cells(transformedITD,ITD-D835V,andITD-F691Lmutations)[1].PF15(1,3,10,30,100,300,1000nM;6h)obviouslyinducesFLT3degradationinadose-dependentmannerand(10,30,100,300,1000nM;6h)dramaticallyinhibitsthephosphorylationofFLT3andSTAT5inBaF3-FLT3-ITDcells[1].PF15(10,30,100,300,1000nM;6h)sharplydownregulatesthephosphorylationofFLT3andSTAT5at100nMinbothBaF3-FLT3-ITD-D835VandBaF3-FLT3-ITD-F691Lcells[1].PF15(100nM;1,3,6,12,24h)inducesFLT3degradationinatime-dependentmannerfrom1hto24h[1].PF15(15.6,31.2,62.5,125,250,500,1000,2000nM;24h)inducesFLT3degradationwithaDC50of76.7nM[1].CellProliferationAssay[1]CellLine:MV4-11,Molm-13,BaF3cells(transformedITD,ITD-D835V,andITD-F691Lmutations)Concentration:0-1000nMIncubationTime:72hResult:Exhibitedanti-proliferationactivitywithIC50sof4.83nM(MV4-11),4.01nM(Molm-13)and7.85,120.1,116.6nM(fortransformedBaF3cellsharboringITD,ITD-D835V,and1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEITD-F691Lmutationsrespectively).WesternBlotAnalysis[1]CellLine:BaF3-FLT3-ITD,BaF3-FLT3-ITD-D835V,BaF3-FLT3-ITD-F691LcellsConcentration:1,3,10,30,100,300,1000nMIncubationTime:6hResult:InducedFLT3degradationwhenat3nMandinadose-dependentmannerinBaF3-FLT3-ITDcells.DramaticallyinhibitedthephosphorylationofFLT3andSTAT5whenconcentrationupto30nMinBaF3-FLT3-ITDcells,andat100nMinbothBaF3-FLT3-ITD-D835VandBaF3-FLT3-ITD-F691Lcells.WesternBlotAnalysis[1]CellLine:BaF3-FLT3-ITDcellsConcentration:100nMIncubationTime:1,3,6,12,24hResult:SignificantlyinducedFLT3degradationinatime-dependentmanner,andFLT3completelydegradedwhenat24h.WesternBlotAnalysis[1]CellLine:BaF3-FLT3-ITDcellConcentration:15.6,31.2,62.5,125,250,500,1000,2000nMIncubationTime:24hResult:NotablyinducedFLT3degradationwhenat125nM,andDC50was76.7nM.體內(nèi)研究PF15(10or20mg/kg;i.p.;oncedailyfor10days)showsgoodtumorgrowthinhibitionwithaninhibitoryrateof58.4%atdosageof10mg/kg,andwhenupto20mg/kgdisplayshigherinhibitoryrate[1].PF15(twicedaily(20mg/kg),oncedaily(40mg/kg);12days;i.p.)prolongsthemediansurvivalupto15days(negativecontrolgroupis11days)inBaF3-FLT3-ITDinsitumodel[1].AnimalModel:FemaleNOD/SCIDmice(BaF3-FLT3-ITDxenograftmodel)[1].Dosage:10or20mg/kgAdministration:Intraperitonealinjection;oncedailyfor10days.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:Achievedgoodtumorgrowthinhibitionwithaninhibitoryrateof58.4%(10mg/kg),meanwhile,whenat20mg/kgdisplayedhigherinhibitoryrate.Hardlycausedsideeffectsonheart,liver,andkidney(bothofthetreatmentgroups).AnimalModel:FemaleBALB/cnudemice(BaF3-FLT3-ITDinsitumodel)[1].Dosage:20,40mg/kgAdministration:Intraperitonealinjection;twicedaily(20mg/kg),oncedaily(40mg/kg);12days.Result:Prolongedthemediansurvivalfrom11daysto15days(bothofthetreatmentgroups).REFERENCES[1].ChenY,etal.DegradingFLT3-ITDproteinbyproteolysistargetingchimera(PROTAC).BioorgChem.2022Feb;119:105508.McePdfHeightCaution: