Osimertinib-d6-AZD-9291-d6-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOsimertinib-d6Cat.No.:HY-15772SCASNo.:1638281-44-3Synonyms:AZD-9291-d6;Mereletinib-d6分⼦式:C₂₈H₂₇D₆N₇O₂分⼦量:505.64作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:4°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)BIOLOGICALACTIVITY⽣物活性OsimertinibD6(AZD-9291D6)氘标记的Osimtinib。Osimtinib⼀种共价结合、具有⼝服活性、不可逆和突变的选择性的EGFR抑制剂，其有效抑制L858R(IC50=12nM)和L858R/T790M(IC50=1nM)EGFR。Osimtinib解决了肺癌T790M突变介导的EGFR抑制剂耐药[1]。体外研究Osimertinib(AZD9291)(0-10μM;72hours)dramaticallyinhibitscellproliferationwithIC50sof41,26,41,and31nM,respectively[2].Osimertinib(0-10μM;72hours)inhibitscellproliferation(Ba/F3cellsharboringaT790Mmutation,exon19del+T790M,orL858R+T790M)withIC50sof6,7,and74nM,respectively[2].Osimertinib(0-10μM;72hours)inhibitsBa/F3cellsharboringEGFRexon20insertionmutations(IC50rangingfrom16-701nMforA763_Y764insFQEA(FQEA),Y764_V765insHH(HH),A767_V769dupASV(ASV),andD770_N771insNPG(NPG)cells)[2].Osimertinibshowshighlevelsofphenotypepotencyinbothsensitizing-mutant(meanIC50of8nMinPC-9)andT790M(meanIC50of11and40nMinH1975andPC-9VanRrespectively)EGFRcelllines.Osimertinibhasmuchlessactivitytowardswild-typeEGFR(meanIC50of650and461nMinCalu3andH2073respectively)[1].Osimertinib(0.1μM;48hours)inducesapoptosisinBa/F3cells(apoptosisrateof40.9%and90%inEGFRexon19del+T790M,EGFRL858R+T790Mrespectively)[2].CellProliferationAssay[2]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:PC-9,H3255,PC-9ER,andH1975cellsConcentration:0.0001,0.001,0.01,0.1,1,10μMIncubationTime:72hoursResult:Dramaticallyinhibitedcellproliferation(IC50=41,26,41,31nM,respectively)CellProliferationAssay[2]CellLine:Ba/F3cells(harboringaT790Mmutation,exon19del+T790M,orL858R+T790M)Concentration:0.0001,0.001,0.01,0.1,1,10μMIncubationTime:72hoursResult:Inhibitedcellproliferation(IC50=6,7,74nM,respectively)ApoptosisAnalysis[2]CellLine:Ba/F3cells(harboringEGFRexon20insertionmutations)Concentration:0.0001,0.001,0.01,0.1,1,10μMIncubationTime:72hoursResult:Inhibitedcellproliferation(IC50=16,701,230,38nM,respectively)ApoptosisAnalysis[2]CellLine:Ba/F3cells(harboringEGFRexon19del+T790MorEGFRL858R+T790M)Concentration:0.1μMIncubationTime:48hoursResult:Inductedapoptosiswiththerateof40.9%and90%inEGFRT790Mpositivemutationscellsrespectively.体内研究Osimertinib(0.1-25mg/kg;p.o.;dailyfor14day)inducessignificantdose-dependentregressioninbothPC-9(ex19del)andH1975(L858R/T790M)tumorxenograftmodels[1].AnimalModel:PC-9(ex19del)andH1975(L858R/T790M)tumorxenograftmodels[1]Dosage:0.1-10mg/kg(PC-9xenograftmodels);0.5-25mg/kg(H1975xenograftmodels)Administration:p.o.;dailyfor14day2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Inducedsignificantdose-dependentregressioninbothPC-9(ex19del)andH1975(L858R/T790M)tumorxenograftmodels.REFERENCES[1].CrossDA,etal.AZD9291,anirreversibleEGFRTKI,overcomesT790M-mediatedresistancetoEGFRinhibitorsinlungcancer.CancerDiscov.2014Sep;4(9):1046-61.[2].[2]HiranoT,etal.PharmacologicalandStructuralCharacterizationsofNaquotinib,aNovelThird-GenerationEGFRTyrosineKinaseInhibitor,inEGFR-MutatedNon-SmallCellLungCancer.MolCancerTher.2018Apr;17(4):740-750.McePdfHeightCaution:Product