EGFR-IN-12-DataSheet-生命科学试剂-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEEGFR-IN-12Cat.No.:HY-17499CASNo.:879127-07-8分⼦式:C₂₁H₁₈F₃N₅O分⼦量:413.4作⽤靶点:EGFR;Apoptosis作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(604.74mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4190mL12.0948mL24.1896mL5mM0.4838mL2.4190mL4.8379mL10mM0.2419mL1.2095mL2.4190mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存⽅式和期限。BIOLOGICALACTIVITY⽣物活性EGFR-IN-12⼀种4,6-⼆取代的嘧啶，⼀种有效的，ATP竞争性，不可逆且⾼度选择性的EGFR抑制剂，IC50为21nM。EGFR-IN-12还抑制突变型EGFRL858R和EGFRL861Q，IC50分别为63nM和4nM。EGFR-IN-12对EGFR的选择性⾼于HER4(IC50=7640nM)和55种其他激酶。EGFR-IN-12诱导细胞凋亡(apoptosis)并具有抗肿瘤活性。IC50&TargetEGFR(WT)EGFRL858REGFRL861QHER41/2MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE21nM(IC50)63nM(IC50)4nM(IC50)7640nM(IC50)体外研究EGFR-IN-12(EGFRinhibitor324674;0-2µM;48hours;HT29andSW480cells)treatmentefficientlyinducesapoptosisatlowerconcentrations[2].EGFR-IN-12(EGFRinhibitor324674;0-3µM;3hours;HT29andSW480cells)treatmentinhibitsEGFRactivationandthedownstreamAKTsignalingpathwayinadose-dependentmanner[2].EGFR-IN-12(EGFRinhibitor324674)inhibitsHT29andSW480cellproliferationwithwithIC50sof1.96µMand1.04µM,respectively[2].PretreatmentofcellswithEGFR-IN-12(compound1;10µM)resultsincompleteinhibitionofwild-typereceptorautophosphorylationinU-2OScells.AndtheT766MmutantreceptoriscompletelyresistanttoinhibitionbyEGFR-IN-12[1].ApoptosisAnalysis[1]CellLine:HT29andSW480cellsConcentration:0µM,1µM,2µMIncubationTime:48hoursResult:InducedapoptosisinHT29cellsandSW480cells.WesternBlotAnalysis[1]CellLine:HT29andSW480cellsConcentration:0µM,0.1µM,0.3µM,1µM,3µMIncubationTime:3hoursResult:InhibitedEGFRactivationandthedownstreamAKTsignalingpathwayinadose-dependentmanner.REFERENCES[1].QiongZhang,etal.DiscoveryofEGFRSelective4,6-disubstitutedPyrimidinesFromaCombinatorialKinase-DirectedHeterocycleLibrary.JAmChemSoc.2006Feb22;128(7):2182-3.[2].ZhiweiYu,etal.NovelIrreversibleEGFRTyrosineKinaseInhibitor324674SensitizesHumanColonCarcinomaHT29andSW480CellstoApoptosisbyBlockingtheEGFRPathway.BiochemBiophysResCommun.2011Aug12;411(4):751-6.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications