EGFR-IN-178-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEEGFR-IN-178Cat.No.:HY-178448分子式:C₂₃H₂₉N₉O₂分子量:463.54作用靶点:EGFR;JAK;Ferroptosis;Apoptosis;ReactiveOxygenSpecies(ROS);CannabinoidReceptor;GlutathionePeroxidase;Caspase作用通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Epigenetics;StemCell/Wnt;Apoptosis;Immunology/Inflammation;MetabolicEnzyme/Protease;NF-κB;GPCR/GProtein;NeuronalSignaling储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性 EGFR-IN-178是一种口服有效的EGFR突变体抑制剂，对EGFR酶突变体具有高度选择性的抑制活性，包括Del19(IC50=3.4nM)、L858R/T790M(IC50=2.9nM)和Del19/T790M(IC50=2.5nM)。EGFR-IN-178对JAK2(IC50=55.6nM)和JAK3(IC50=46.1nM)激酶也具有良好的活性。EGFR-IN-178能够增加细胞内脂质氧化物丙二醛(MDA)的含量，同时降低谷胱甘肽(GSH)的含量，最终导致癌细胞发生铁死亡(ferroptosis)。EGFR-IN-178通过增加裂解caspase-3的表达来促进细胞凋亡(apoptosis)。EGFR-IN-178能够抑制EGFR蛋白的磷酸化，降低JAK2的活性形式p-JAK2，从而诱导细胞内活性氧(ROS)的增加。EGFR-IN-178可用于非小细胞肺癌(NSCLC)的研究[1]。IC50&TargetJAK2JAK3Caspase355.6nM(IC50)46.1nM(IC50)体外研究EGFR-IN-178(Compound14a)(1-100nM,pretreatedfor72hours,followedbyculturingfor10–14days)withIC50valuesof18.5nMforH1975-EGFRL858R/T790Mand15.4nMforPC9-EGFRDel19,showingsignificantefficacyat5nMonPC9-EGFRDel19cells,atapproximately10nMonH1975-EGFRL858R/T790Mcells,andnoinhibitionevenat100nMonA549-EGFRWTcells[1].EGFR-IN-178(50-100nM,24h)canenhancegreenfluorescenceofH1975-EGFRL858R/T790Mcells,indicatingthatEGFR-IN-178canleadtoanincreaseinintracellularROS[1].EGFR-IN-178(10-100nM)inhibitsthephosphorylationofEGFRwithoutreducingitstotalproteincontentinH1975-EGFRL858R/T790Mcells.ItconcurrentlysuppressestheJAK2-STAT3signalingpathwaybysignificantlydecreasingp-JAK2levelsat100nMandp-STAT3levelsat50nM,whichisconsistentwithits1/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEinhibitoryeffectonJAK2-3kinaseactivity[1].EGFR-IN-178(5-100nM,24h)inducesferroptosisinH1975-EGFRL858R/T790Mcells,asevidencedbyincreasedlevelsoflipidperoxides(MDA),ironions(Fe2+),andoxidizedlipids(greenfluorescence),alongsidedecreasedglutathione(GSH)andGPX4levels,whileitalsopromotesapoptosisbyincreasingcleavedcaspase-3expression[1].EGFR-IN-178(10-50nM,12-24h)caneffectivelyinhibittheinvasionandmigrationofH1975-EGFRL858R/T790Mcellsinaconcentration-dependentmanner[1].EGFR-IN-178showsnosignificanttoxicitytoHUVECs,HK-2,Hacat,andmouse-derivedC2C12(muscletissue)andNIH3T3(embryonicfibroblasts)[1].CellProliferationAssay[1]CellLine:A549cells,PC9-EGFRDel19cells,H1975-EGFRL858R/T790MConcentration:1nM,5nM,10nM,50nM,100nMIncubationTime:Pretreatedfor72hours,followedbyculturingfor10–14daysResult:Showedsignificantinhibitionat5nMonPC9-EGFRDel19cells,atapproximately10nMonH1975-EGFRL858R/T790Mcells,andnoinhibitionevenat100nMonA549cells.CellInvasionAssay[1]CellLine:H1975-EGFRL858R/T790MConcentration:10nM,50nMIncubationTime:72hResult:EffectivelyinhibitedtheinvasionofH1975-EGFRL858R/T790Mcells.CellMigrationAssay[1]CellLine:H1975-EGFRL858R/T790MConcentration:10nM,50nMIncubationTime:12hResult:EffectivelyinhibitedthemigrationofH1975-EGFRL858R/T790Mcells.体内研究EGFR-IN-178(10mg/kg,p.o.,oncedailyfor13days)exhibitspotentantitumoractivity,withoutsignificantweightloss,andnoabnormalitiesinmentalstate,diet,orbehaviorinH1975-EGFRL858R/T790Mxenograftmice[1].AnimalModel:Usinga1mLsterilesyringe,0.2mLofH1975-EGFRL858R/T790Mcellsuspensionwithaconcentrationof5×10^7/mLwasdrawnandinjectedintotherightarmpitofeachmalenudemouse(4-week-old)[1].2/3 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEDosage:10mg/kgAdministration:P.o.,oncedailyfor13daysResult:HadaTGIof90%(tumorgrowthinhibitionratebyweight).Nosignificantweightlossinthenudemice.Mentalstatewasnormal,andnoabnormalitiesintheireatingandbehavior.REFERENCESYaoH,etal.ThesynthesisandevaluationofnewN-(pyrazin-2-yl)-4-aminopyrimidinederivativestargetedEGFRandJAK.EurJMedChem.2025Dec15;300:1181