Osimertinib-mesylate-AZD-9291-mesylate-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOsimertinibmesylateCat.No.:HY-15772ACASNo.:1421373-66-1Synonyms:AZD-9291mesylate;Mereletinibmesylate分?式:C??H??N?O?S分?量:595.71作?靶點(diǎn):EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:13.89mg/mL(23.32mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.6787mL8.3933mL16.7867mL5mM0.3357mL1.6787mL3.3573mL10mM0.1679mL0.8393mL1.6787mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.39mg/mL(2.33mM);Clearsolution1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.39mg/mL(2.33mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.39mg/mL(2.33mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)simertinibmesylate(AZD-9291mesylate)不可逆的突變體選擇性EGFR抑制劑；對(duì)EGFRL858R和EGFRL858R/T790M的IC50值分別為12和1nM。IC50&TargetEGFRL858R/T790MEGFRL858R1nM(IC50)12nM(IC50)體外研究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?邊的抑制劑?師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.體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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?邊的抑制劑?師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