Description:

Epidermalgrowthfactorreceptor(EGFR)isacell-surfacereceptorwithintrinsicintracellularprotein-tyrosinekinase(TK)activity.LigandbindinginducesEGFRdimerizationandphosphorylation,leADIngtotheactivationofEGFRsignalingpathway.Inseveralmalignanciessuchasnon-smallcelllungcancer(NSCLC),EGFRsignalingisderegulatedduetomutationsinEGFR,whichresultsinuncontrolledproliferationandmigrationoftumorcells.EGFRmutationscanleadto“oncogene-addicted”cancers,wherethetumorcellsdependonthemutatedEGFRforcellsurvivalandmalignantphenotype. OneofthemostcommonEGFRmutationsfoundinhumanpatientsisL858Rsubstitutioninexon21,withintheactivationloopofEGFR.PatientswiththismutationaresensitivetoEGFRtyrosinekinaseinhibitors(TKIs)suchasgefitiniborerlotinib,whereaspatientswithwildtypeEGFRarenotsensitivetoTKI.AnotherclinicallyrelevantmutationassociatedwithacquiredgefitinibanderlotinibresistanceisT790M,foundinexon20.CellsexpressingEGFRwithbothL858RandT790Mmutationsareresistanttoinducedapoptosisinthepresenceofgefitiniborerlotinib. 

Data:

 

Dose-dependentgrowthinhibitionofBaF3cellsharboringEGFRDel19(EL-011),EGFRIns19(EL-009)andrepresentativeErlotinibresistantcellline,EGFRDel19-T790M(EL-014).Thecellsweretreatedwiththeindicateddoseoferlotinibfor24hoursandcellsviABIlitywasmeasuredusingSignosisCVCreagent.EGFRDel19stablyexpressingBaF3cells(EL-011)remains14-foldmoresensitivetoTKIerlotinib(IC50=0.34)thanitsresistancederivativeEGFRDel19-T790MstablyexpressingBaF3cells(EL-014)(IC50=4.9).

 

Signosis 是一家专业的生物分析供应商，致力于基于微孔板分析技术的生命科学研究产品的开发、生产和销售。Signosis 成立于2007年，坐落于世界研发中心--美国硅谷的中心地带。公司专注于细胞因子、转录因子、miRNA及疾病标志物等重要调控因子和标志物的研究，基于自有专利技术，开发完成400多种先进而独特的用于发现、筛选和分析的生命科学研究产品。Signosis 产品销售遍布北美、欧洲、亚洲及中东等主要国家和地区，客户涵盖美国国立卫生研究院、哈佛大学、耶鲁大学等著名研究机构以及众多制药公司