Hotline:400-820-3792Inhibitors ? ScreeningLibraries ? Proteinswww.MedChemEEGFR-IN-181Cat.No.:HY-178939分子式:C??H??ClN?OP分子量:482.95作用靶點:EGFR;Akt;PERK;Apoptosis作用通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;PI3K/Akt/mTOR;CellCycle/DNADamage;Apoptosis儲存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 EGFR-IN-181是一種具有口服活性，可穿透血腦屏障的強(qiáng)效EGFRL858R/T790M/C797S三重突變抑制劑(IC501.32nM)。EGFR-IN-181可抑制EGFR磷酸化(p-EGFR)及其下游信號蛋白AKT(p-AKT)和ERK(p-ERK)的磷酸化。EGFR-IN-181可誘導(dǎo)細(xì)胞凋亡(apoptosis)并導(dǎo)致G2期阻滯。EGFR-IN-181可用于非小細(xì)胞肺癌(NSCLC)和腦轉(zhuǎn)移瘤的研究[1]。IC50&TargetAktEGFR(C797S/T790M/L858R)體外研究EGFR-IN-181(CompoundD18)(0.001-1000μg/mL,48h)showssignificantanti-proliferativeactivityagainstvariousEGFRmutantcelllinesandhasahighIC50againstnormalcells(MCR-5,HEK293,LX-2)[1].EGFR-IN-181(50-500nM,24h)concentration-dependentlyinhibitsEGFRphosphorylation(p-EGFR)anditsdownstreamsignalingproteinsAKT(p-AKT)andERK(p-ERK)inNCI-H1975cells(carryingEGFRL858R/T790M/C797S)[1].EGFR-IN-181(50-500nM,24h)concentration-dependentlyinducesapoptosisinNCI-H1975EGFRL858R/T790M/C797ScellsandcausesG2phasearrest[1].EGFR-IN-181inhibitshERGpotassiumchannelsinHEK293cellswithanIC50of10.55μM[1].CellProliferationAssay[1]CellLine:A549cellline:harboringEGFRWTBaF3?cellline:engineeredBaF3cellline,harboringEGFRL858R/T790M/C797SNCI–H1975cellline:harboringEGFRL858R/T790M/C797SPC-9cellline:harboringEGFRDel19H1975cellline:harboringEGFRL858R/T790MMCR-5,HEK293,LX-2Concentration:0.001μg/mL,0.01μg/mL,0.1μg/mL,1μg/mL,10μg/mL,100μg/mL,1000μg/mL1/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEIncubationTime:48hResult:A549(IC50=2.63μM)PC-9(IC50=0.012μM)H1975(IC50=0.027μM)BaF3TM(IC50=0.049μM)NCI–H1975(IC50=0.87μM)MCR-5(IC50=4.51μM)HEK293(IC50=36.17μM)LX-2(IC50=4.84μM)WesternBlotAnalysis[1]CellLine:NCI-H1975EGFRL858R/T790M/C797SConcentration:50nM,100nM,500nMIncubationTime:24hResult:Concentration-dependentlyinhibitedEGFRphosphorylation(p-EGFR)anditsdownstreamsignalingproteinsAKT(p-AKT)andERK(p-ERK)inNCI-H1975cellsEGFRL858R/T790M/C797S;ataconcentrationof500nM,EGFRphosphorylationwascompletelyinhibited.ApoptosisAnalysis[1]CellLine:NCI-H1975EGFRL858R/T790M/C797ScellsConcentration:50nM,150nM,250nM,500nMIncubationTime:24hResult:Inducedapoptosisinadegree-dependentmanner,achievinganapoptosisrateof37.94%ataconcentrationof500nM.CellCycleAnalysis[1]CellLine:NCI-H1975EGFRL858R/T790M/C797ScellsConcentration:50nM,150nM,250nM,500nMIncubationTime:24hResult:InducedG2phasearrestinaconcentration-dependentmanner,withtheproportionofcellsinG2phasebeing22.57%at50nMandincreasingto65.98%at500nM.體內(nèi)研究EGFR-IN-181(CompoundD18)(12.5-25mg/kg,p.o.,oncedailyfor15days)significantlyinhibitsthegrowth2/3 MasterofBioactiveMolecules—您身邊的抑制劑大師www.MedChemEofEGFR-mutanttumorsinNCI-H1975cellsEGFRL858R/T790M/C797Sxenograftmiceinadose-dependentmanner,demonstratinggoodsafetyandtolerabilitywithnosignificanttoxicity[1].AnimalModel:AxenografttumormodelwasestablishedusingfemaleBALB/cnudemice(6-8weeksold)bysubcutaneoustransplantationofNCI-H1975cellsEGFRL858R/T790M/C797Striplemutations)[1].Dosage:12.5mg/kg,25mg/kgAdministration:P.o.,oncedailyfor15daysResult:Atadoseof12.5mg/kg,thetumorgrowthinhibitionrate(TGI)was53.64%;atadoseof25mg/kg,theTGIwas91.04%.Theaveragetumorweightwassignificantlylowerthanthatofthecontrolgroup.Didnotexperienceasignificantdecreaseinbodyweight,andH&Estainingofthemajororgans(heart,liver,spleen,lung,andkidney)showednolesionsororganfailure.REFERENCESZhaoL,etal.Discoveryofabrain-penetrantfourth-generationEGFRinhibitortoovercomethehumantriple(L858R/T790M/C797S)mutation.EurJMedChem.2025Oct14;302(Pt1):118256.McePdfH