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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/AZD-9291（同义词：奥西米替尼；Mereletinib）/HY-15772/10mM*1mL二甲基亚砜
商品详细Medchemexpress/AZD-9291（同义词：奥西米替尼；Mereletinib）/HY-15772/10mM*1mL二甲基亚砜
Medchemexpress/AZD-9291（同义词：奥西米替尼；Mereletinib）/HY-15772/10mM*1mL二甲基亚砜
Medchemexpress/AZD-9291（同义词：奥西米替尼；Mereletinib）/HY-15772/10mM*1mL二甲基亚砜
商品编号： HY-15772-10mM*1mLinDMSO
品牌： MedChemExp
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产地： 美国(厂家直采)
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产品分类： 小分子
公司分类： Small_molecule
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商品介绍
AZD-9291isanirreversIBLeandmutantselectiveEGFRinhibitorwithIC50sof12and1nMagainstEGFRL858RandEGFRL858R/T790M,respectively.

CustomerValidation

  • •JMedChem.2017Apr13;60(7):2944-2962.
  • •Oncotarget.2017Mar14;8(11):18359-18372.
  • •Oncotarget.2016Oct25;7(43):69760-69769.
  • •Oncotarget.2015Oct13;6(31):31313-22.
  • •GenesCancer.2017Mar;8(3-4):497-504.
Description

AZD-9291isanirreversibleandmutantselectiveEGFRinhibitorwithIC50sof12and1nMagainstEGFRL858RandEGFRL858R/T790M,respectively.

IC50&Target

IC50:1nM(EGFRL858R/T790M),12nM(EGFRL858R)[1]

InVitro

AZD-9291(AZD9291)showssimilarpotencytoearlygenerationtyrosinekinaseinhibitor(TKIs)ininhibitingEGFRphosphorylationinEGFRcellsharboringsensitisingEGFRmutantsincludingPC-9(ex19del),H3255(L858R)andH1650(ex19del),withmeanIC50valuesrangingfrom13to54nMforAZD-9291.AZD-9291alsopotentlyinhibitsphosphorylationofEGFRinT790Mmutantcelllines(H1975(L858R/T790M),PC-9VanR(ex19del/T790M),withmeanIC50potencylessthan15nM[1].

InVivo

Thetumor-bearingmicearetreatedwithAZD-9291(5mg/kg/day)foronetotwoweeks.Withindaysoftreatment,5of5C/L858Rmicedisplaysnearly80%reductionintumorvolumebymagneticresonanceimagingMRIaftertherapywithAZD-9291,while5of5micetreatedwithvehicleshowstumorgrowth[1].AZD-9291demonstratesimprovedratPK,reducedhERGaffinity,andimprovedIGF1Rmarginsrelativetothepreviouslydescribedcompounds,andsothiscompoundisselectedforfurtherinvestigation.AZD-9291alsooffersanadditionaldegreeofbroaderchemicalandprofilediversitywhencomparedtothepreviouslydescribedleadcompounds.UpondosingAZD-9291inthreeefficacymodels,Thecomparableefficacyisobservedatrelativelylowdoses(10mg/kgperday).TheexcellentefficacyisalsoobservedwhenAZD-9291isdosedat5mg/kgperday[2].

ClinicalTrial
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References

  • [1].CrossDA,etal.AZD9291,anirreversibleEGFRTKI,overcomesT790M-mediatedresistancetoEGFRinhibitorsinlungcancer.CancerDiscov.2014Sep;4(9):1046-61.

    [2].FinlayMR,etal.DiscoveryofapotentandselectiveEGFRinhibitor(AZD9291)ofbothsensitizingandT790Mresistancemutationsthatsparesthewildtypeformofthereceptor.JMedChem.2014Oct23;57(20):8249-67.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.0016mL10.0078mL20.0156mL
5mM0.4003mL2.0016mL4.0031mL
10mM0.2002mL1.0008mL2.0016mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

AZD-9291isdissolvedinDMSOandstored,andthendilutedwithappropriatemediumbeforeuse[1].

PC-9cellsareseededintoT75flasks(5×105cells/flask)inRPMIgrowthmediaandincubatedat37°C,5%CO2.ThefollowingdaythemediaisreplacedwithmediasupplementedwithaconcentrationofEGFRinhibitorequaltotheEC50concentrationpredeterminedinPC-9cells.Mediachangesarecarriedoutevery2-3daysandresistantclonesallowedtogrowto80%confluencypriortothecellsbeingtrypsinisedandreseededattheoriginalseedingdensityinmediacontainingtwicetheconcentrationofEGFRinhibitor.Doseescalationsarecontinueduntilafinalconcentrationof1.5μMGefitinib,1.5μMAfatinib,1.5μMWZ4002or160nMAZD-9291areachieved[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdmiNISTration
[1][2]

AZD-9291issUSPendedin1%Polysorbate80(Mice)[1].
AZD-9291issuspendedin0.5%w/vHPMC/0.1%w/vTweenindeionizedwaterataconcentrationof20mg/mL(Rat)[2].

Mice[1]
TheEGFRL858RandEGFRL858R+T790Mmice(maleandfemale)areused.AZD-9291issuspendedin1%Polysorbate80andadministeredviaoralgavageoncedailyatthedosesof7.5mg/kgand5mg/kg,respectively.MiceareimagedweeklyattheVanderbiltUniversityInstituteofImagingScience.Forimmunoblotanalysis,micearetreatedforeighthourswithdrugasdescribedbeforedissectionandflashfreezingofthelungs.Lungsarepulverizedinliquidnitrogenbeforelysis.
Rat[2]
ThemaleRccHan:WISTrats(10-week-old)arereceivedasingleoraldoseofAZD-9291(200mg/kg).BloodglucoselevelsaremeasuredusinganAccuchekActivemeter.SeruminsulinconcentrationsaredeterminedusingacommercialratELISAkit.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].CrossDA,etal.AZD9291,anirreversibleEGFRTKI,overcomesT790M-mediatedresistancetoEGFRinhibitorsinlungcancer.CancerDiscov.2014Sep;4(9):1046-61.

    [2].FinlayMR,etal.DiscoveryofapotentandselectiveEGFRinhibitor(AZD9291)ofbothsensitizingandT790Mresistancemutationsthatsparesthewildtypeformofthereceptor.JMedChem.2014Oct23;57(20):8249-67.

MolecularWeight

499.61

Formula

C₂₈H₃₃N₇O₂

CASNo.

1421373-65-0

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥30mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:99.95%