Neratinib-maleate-HKI-272-maleate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENeratinibmaleateCat.No.:HY-32721BCASNo.:915942-22-2Synonyms:HKI-272maleate分⼦式:C₃₄H₃₃ClN₆O₇分⼦量:673.11作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性Neratinib(HKI-272)maleate⼀种具有⼝服活性的、不可逆的、⾼选择性的HER2和EGFR抑制剂，IC50值分别为59nM和92nM。IC50&TargetHER2EGFR59nM(IC50)92nM(IC50)体外研究Neratinibdisplaysnoactivityagainstotherserine-threoninekinasessuchasAkt,cyclinD1/cdk4,cyclinE/cdk2,cyclinB1/cdk1,IKK-2,MK-2,PDK1,c-Raf,andTpl-2,aswellasthetyrosinekinasec-Met[1].Neratinib(0.5ng/mL–5μg/mL,2days)inhibitstheproliferationofcelllinesthatshowhighlevelsofHER-2(3T3/neu,SK-Br-3,andBT474)andismuchlessactiveincelllinesthatexpressneitherHER-2norEGFR(3T3,MDA-MB-435,andSW620)[1].Neratinib(0-2nM,12-16h)arrestsBT474cellcycleatG1-Sphase[1].NeratinibresultsintheinhibitionofMAPKandAktphosphorylation,down-regulationofcyclinD1levels,andinductionofp27[1].CellProliferationAssay[1]CellLine:3T3,3T3/neu,SK-Br-3,BT474,A431,MDA-MB-435andSW620Concentration:0.5ng/mL–5μg/mLIncubationTime:2days(6daysforBT474)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:InhibitedcellproliferationwithIC50valuesof700±78,3±0.14,2±0.18,2±0.06,81±9,960±165and690±84nMagainst3T3,3T3/neu,SK-Br-3,BT474,A431,MDA-MB-435andSW620cells,respectively.WesternBlotAnalysis[1]CellLine:BT474orA431cellsConcentration:0,2,10,50,100and200nMIncubationTime:3hResult:Decreasedligand-independentreceptorphosphorylationby50%(IC50)at5nMinBT474cells,repressedEGF-dependentphosphorylationofEGFRinA431cellsatacomparabledose(IC50=3nM).EffectivelyrepressedphosphorylationofMAPKandAktinBT474cells.CellCycleAnalysis[1]CellLine:BT474Concentration:0–2nMIncubationTime:12–16hResult:Blockedcellcycleprogression,causingaG1-Sarrest,a50%decreaseinthenumberofcellsintheS(DNAsynthesis)phaseofthecellcyclewasobservedataconcentrationof2nM.体内研究Neratinib(HKI-272)(0-80mg/kg/day;i.g.;42days)showsanticanceractivitiesagainstcancercellsthatexpresseshighlevelsofHER-2orEGFR[1].AnimalModel:Femaleathymic(nude)mice,tumorxenograft[1]Dosage:10,20,40,60or80mg/kg/dayAdministration:Gavage,42daysResult:Reducedtumorgrowthinadose-dependentmannerin3T3/neu,BT474,SK-OV-3andA431xenografts,butwasoinactiveinxenograftsofMX-1andMCF-7.InhibitedphosphorylationofHER-2inBT474xenografts.户使⽤本产品发表的科研⽂献•AnnRheumDis.2020Dec;79(12):1635-1643.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•SciTranslMed.2018Jun20;10(446):eaao2565.•CellSyst.2019Jul24;9(1):35-48.e5.•CellRep.2022Apr5;39(1):110595.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RabindranSK,etal.AntitumoractivityofHKI-272,anorallyactive,irreversibleinhibitoroftheHER-2tyrosinekinase.CancerRes,2004,64(11),3958-3965.McePdfHeightCaution:Producthasnotbeenfully