Afatinib-oxalate-BIBW-2992-oxalate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAfatiniboxalateCat.No.:HY-10261DCASNo.:1398312-64-5Synonyms:BIBW2992oxalate分⼦式:C₂₆H₂₇ClFN₅O₇分⼦量:575.97作⽤靶点:EGFR;Autophagy;Apoptosis;c-Met/HGFR;Akt作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Autophagy;Apoptosis;PI3K/Akt/mTOR储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Afatinib(BIBW2992)oxalate⼀种⼝服有效且不可逆的ErbB家族(EGFR和HER2)双特异性抑制剂，对EGFRwt,EGFRL858R,EGFRL858R/T790M和HER2的IC50值分别为0.5nM、0.4nM、10nM和14nM。Afatiniboxalate可⽤于⾷管鳞状细胞癌(ESCC)、⾮⼩细胞肺癌(NSCLC)和胃癌的研究。IC50&TargetEGFRL858REGFRWTEGFRL858R/T790MHER20.4nM(IC50)0.5nM(IC50)10nM(IC50)14nM(IC50)HER3pAKT体外研究Afatiniboxalate(100nM)sufficientlypreventsheregulin-stimulatedHER3phosphorylation[1].Afatiniboxalate(0-10000nM)effectivelyinhibitsanchorage-independentproliferationofNIH-3T3cellsectopicallyexpressingEGFRmutants,andinhibitscellproliferationofH1666,H3255,andNCI1975cells[1].Afatiniboxalate(48-72h)showsgrowthinhibitioninHKESC-1,HKESC-2,SLMT-1andEC-1cells[2].Afatiniboxalate(0-1μM,24-48h)inhibitsAKTandMAPKpathways,andinhibitsEGFRandAKTphosphorylationinESCCcelllines[2].Afatiniboxalate(0-1μM,16-48h)inducesG0/G1cellcyclearrestinHKESC-2andEC-1[2].Afatiniboxalate(0-1μM,24-48h)effectivelyinducesapoptoticcelldeathinHKESC-2andEC-1[2].CellProliferationAssay[1]CellLine:NIH-3T3cells,H1666,H3255,andNCI1975cells1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:0,1,10,100,1000,10000nMIncubationTime:Result:Effectivelyinhibitedanchorage-independentproliferationofNIH-3T3cellsectopicallyexpressingEGFRmutants.Showedinhibitionofanchorageindependentcellproliferationofvariouslungcancercelllines(H1666,H3255,andNCI1975cells),withIC50valuesof60nM,0.7nMand99nM,respectively.CellViabilityAssay[2]CellLine:HKESC-1,HKESC-2,SLMT-1andEC-1celllinesConcentration:IncubationTime:48and72hoursResult:Observedover95%ofgrowthinhibition.TherespectiveIC50concentrationsat48hours(HKESC-1=0.078μM,HKESC-2=0.115μM,KYSE510=3.182μM,SLMT-1=4.625μMandEC-1=1.489μM)and72hours(HKESC-1=0.002μM,HKESC-2=0.002μM,KYSE510=1.090μM,SLMT-1=1.161μMandEC-1=0.109μM)wereallinlowermicro-molarrange.WesternBlotAnalysis[2]CellLine:HKESC-2cellsandEC-1cellsConcentration:0,0.01,and0.1μM(HKESC-2cells),0,0.1and1μM(EC-1cells)IncubationTime:24and48hoursResult:ReducedthephosphorylationofEGFRandtheendogenousexpressionlevelofHER2receptorsinESCCcells.SuppressedAKTphosphorylationinadoseandtimedependentmanner.SignificantlyreducedthephosphorylationlevelofthedownstreameffectorsoftheAKT-mTORaxisespeciallyinHKESC-2cells.InhibitedthetwomajordownstreampathwaysoftheErbB/HERaxis,namely,AKTandMAPKpathwaysinESCCcelllines.CellCycleAnalysis[2]CellLine:HKESC-2cellsandEC-1cellsConcentration:0,0.01,and0.1μM(HKESC-2cells),0,0.1and1μM(EC-1cells)IncubationTime:16,24,and48hoursResult:InducedG0/G1cellcyclearrestinbothtestedESCCcelllinesinatimeanddosedependentmanner.InHKESC-2cells,thepercentageofcellsinG0/G1phasewas2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEincreasedfrom38.2%to68.1%at0.01μMofafatinibandto74.7%at0.1μMofafatinib,from24hours(82.4%G0/G1arrestat0.01μMand86.2%at0.1μM)to48hours(from74.7%to88.2%for0.01μMand91.0%for0.1μM).InEC-1cells,thepercentageofcellsarrestedintheG0/G1phasewasincreasedfrom59.1%to66.6%and72.2%at24and48hoursrespectively.ApoptosisAnalysis[2]CellLine:HKESC-2cellsandEC-1cellsConcentration:0,0.01,and0.1μM(HKESC-2cells),0,0.1and1μM(EC-1cells)IncubationTime:24and48hoursResult:EffectivelyinducedcelldeathbytriggeringapoptoticmechanismsinESCCcelllines.ShowedastrongerexpressionlevelofcleavedPoly(ADP-ribose)polymerase(PARP)inthesecelllines.体内研究Afatiniboxalate(0-20mg/kg,Orally,dailyfor25days)showsdramatictumorregressionanddownregulationofEGFR,HER2,HER3andAKTphosphorylation[1].Afatiniboxalate(15mg/kg,Orally,inascheduleof5daysonplus2daysoff,fortwoweeks)stronglyinhibitsthegrowthofHKESC-2tumor[2].AnimalModel:AthymicNMRI-nu/nufemalemice(21–31g,fivetosix-week-old,transgenicmurinelungcancermodelandxenograftmodels)[1]Dosage:15mg/kg,20mg/kgAdministration:Orally,dailyfor25daysResult:Resultedindramatictumorregressionwithacumulativetreated/controltumorvolumeratio(T/Cratio)of2%inastandardxenograftmodeloftheepidermoidcarcinomacelllineA431,anddownregulationofEGFRandAKTphosphorylation.InducedregressionoflargetumorsinthisHER2-drivenmodel,effectivelycontrolledxenografttumorformationbytheNCIH1975cellline,expressingEGFRL858R/T790M,withaT/Cvalueof12%fordosesof20mg/kg.Inducedmorethan50%percenttumorreductionaftera4-weektreatmentperiod.DownregulatedEGFR,HER2andHER3phosphorylation.AnimalModel:Sixweeksoldfemaleathymicnudemice(nu/nu)(16-20g)[2]Dosage:15mg/kgAdministration:Oralgavageinascheduleof5daysonplus2daysoff,fortwoweeksResult:StronglyinhibitedthegrowthofHKESC-2tumor.Averagetumorsizesofvehicleand3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEtreatmentatendpointare348±24mm3and108±36mm3respectively.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•NatCommun.2019Apr18;10(1):1812•Biomaterials.16September2022.•JPharmAnal.2019Feb;9(1):49-54.•CancerRes.2021Sep15;81(18):4822-4834.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiD,etal.BIBW2992,anirreversibleEGFR/HER2inhibitorhighlyeffectiveinpreclinicallungcancermodels.Oncogene.2008Aug7;27(34):4702-11.[2].WongCH,etal.