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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEOsimertinibmesylateCat.No.:HY-15772ACASNo.:1421373-66-1Synonyms:AZD-9291mesylate;Mereletinibmesylate分⼦式:C₂₉H₃₇N₇O₅S分⼦量:595.71作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:13.89mg/mL(23.32mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6787mL8.3933mL16.7867mL5mM0.3357mL1.6787mL3.3573mL10mM0.1679mL0.8393mL1.6787mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.39mg/mL(2.33mM);Clearsolution1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.39mg/mL(2.33mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.39mg/mL(2.33mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Osimertinibmesylate(AZD-9291mesylate)不可逆的突变体选择性EGFR抑制剂；对EGFRL858R和EGFRL858R/T790M的IC50值分别为12和1nM。IC50&TargetEGFRL858R/T790MEGFRL858R1nM(IC50)12nM(IC50)体外研究Osimertinib(AZD-9291)showssimilarpotencytoearlygenerationtyrosinekinaseinhibitor(TKIs)ininhibitingEGFRphosphorylationinEGFRcellsharboringsensitisingEGFRmutantsincludingPC-9(ex19del),H3255(L858R)andH1650(ex19del),withmeanIC50valuesrangingfrom13to54nMforOsimertinib.Osimertinib(AZD-9291)alsopotentlyinhibitsphosphorylationofEGFRinT790Mmutantcelllines(H1975(L858R/T790M),PC-9VanR(ex19del/T790M),withmeanIC50potencylessthan15nM[1].CellProliferationAssay[2]CellLine: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)CellProliferationAssay[2]CellLine:Ba/F3cells(harboringEGFRexon20insertionmutations)Concentration:0.0001,0.001,0.01,0.1,1,10μMIncubationTime:72hours2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Inhibitedcellproliferation(IC50=16,701,230,38nM,respectively)ApoptosisAnalysis[2]CellLine:Ba/F3cells(harboringEGFRexon19del+T790MorEGFRL858R+T790M)[2]Concentration:0.1μMIncubationTime:48hoursResult:Inductedapoptosiswiththerateof40.9%and90%inEGFRT790Mpositivemutationscellsrespectively.体内研究Thetumor-bearingmicearetreatedwithOsimertinib(AZD-9291)(5mg/kg/day)foronetotwoweeks.Withindaysoftreatment,5of5C/L858Rmicedisplaysnearly80%reductionintumorvolumebymagneticresonanceimagingMRIaftertherapywithOsimertinib,while5of5micetreatedwithvehicleshowstumorgrowth[1].Osimertinib(AZD-9291)demonstratesimprovedratPK,reducedhERGaffinity,andimprovedIGF1Rmarginsrelativetothepreviouslydescribedcompounds,andsothiscompoundisselectedforfurtherinvestigation.Osimertinib(AZD-9291)alsooffersanadditionaldegreeofbroaderchemicalandprofilediversitywhencomparedtothepreviouslydescribedleadcompounds.UpondosingOsimertinib(AZD-9291)inthreeefficacymodels,Thecomparableefficacyisobservedatrelativelylowdoses(10mg/kgperday).TheexcellentefficacyisalsoobservedwhenOsimertinib(AZD-9291)isdosedat5mg/kgperday[2].AnimalModel:PC-9(ex19del)andH1975(L858R/T790M)tumorxenograftmodels[1]Dosage:0.1-10mg/kg(PC-9xenograftmodels);0.5-25mg/kg(H1975xenograftmodels)Administration:p.o.;dailyfor14dayResult:Inducedsignificantdose-dependentregressioninbothPC-9(ex19del)andH1975(L858R/T790M)tumorxenograftmodels.户使⽤本产品发表的科研⽂献•CancerCell.2020Jan13;37(1):104-122.e12.•CancerDiscov.2019Jul;9(7):926-943.•NatCancer.2022Apr;3(4):402-417.•ACSNano.2022Jul21.•JPharmAnal.2021Jun19.Seemorecustomervalidationsonwww.MedChemEREFERENCES3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].CrossDA,etal.AZD9291,anirreversibleEGFRTKI,overcomesT790M-mediatedresistancetoEGFRinhibitorsinlungcancer.CancerDiscov.2014Sep;4(9):1046-61.[2].[2]HiranoT,etal.PharmacologicalandStructuralCharacterizationsofNaquotinib,aNovelThird-GenerationEGFRTyrosineKinaseInhibitor,inEGFR-MutatedNon-SmallCellLungCance