Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEGFR-IN-176Cat.No.:HY-178057CASNo.:2754394-10-8分?式:C??H??N??O?S分?量:699.87作?靶點(diǎn):EGFR;Akt;Anaplasticlymphomakinase(ALK)作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;PI3K/Akt/mTOR儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性EGFR-IN-176?種?服活性且ATP競爭性的EGFR突變體抑制劑(特別C797S介導(dǎo)的EGFR三重突變體)。EGFR-IN-176對三重突變細(xì)胞的?長具有?度選擇性抑制作?，包括Ba/F3EGFR19del/T790M/C797S(IC50=0.001nM)和Ba/F3EGFRL858R/T790M/C797S(IC50=0.04nM)。EGFR-IN-176能夠有效抑制Ba/F3和PC-9細(xì)胞(分別表達(dá)EGFR19del/T790M/C797S或EGFRL858R/T790M/C797S突變)中AKT信號通路的活化，且該抑制作?呈現(xiàn)劑量依賴性。EGFR-IN-176選擇性抑制攜帶EGFR三重突變的細(xì)胞系中的EGFR信號傳導(dǎo)，對表達(dá)野?型EGFR的A431細(xì)胞?抑制作?。EGFR-IN-176可有效抑制ALK的酶活性(IC50<0.5nM)。EGFR-IN-176在??實(shí)驗(yàn)中有效抑制腫瘤?長，并顯?出良好的抗??細(xì)胞肺癌作?[1]。體外研究EGFR-IN-176(Compound31r,0.0045nM-10,000nM,48h)exhibitsextremelypotentandselectivegrowthinhibitoryactivityagainstcellsharboringEGFRtriplemutationinvitro,includingBa/F3EGFR19del/T790M/C797S(IC50=0.001nM)andBa/F3EGFRL858R/T790M/C797S(IC50=0.04nM),withlowcytotoxicitytowardswild-typeEGFRcellsA431(IC50>10,000nM)[1].EGFR-IN-176(500nM,7days)inhibitsPC-9EGFR19del/T790M/C797SandPC-9EGFRL858R/T790M/C797Sproliferationintheshorttermanddeprivescancercellsoftheirself-renewalandclonogenicgrowthcapabilitiesinthelongterm[1].EGFR-IN-176(250nM,0-24h)caneffectivelyinhibitthemigrationabilityofPC-9EGFR19del/T790M/C797SandPC-9EGFRL858R/T790M/C797S[1].EGFR-IN-176(500nM,48h)caninducePC-9EGFR19del/T790M/C797SandPC-9EGFRL858R/T790M/C797Sapoptosis[1].CellViabilityAssay[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:Ba/F3EGFR19del/T790M/C797SandBa/F3EGFRL858R/T790M/C797SConcentration:0.0045nM~10,000nMIncubationTime:48hResult:Exhibitedhigheractivity,withIC50valuesof0.001nM(Ba/F3EGFR19del/T790M/C797S)and0.04nM(Ba/F3EGFRL858R/T790M/C797S)CellMigrationAssay[1]CellLine:PC-9EGFR19del/T790M/C797SandPC-9EGFRL858R/T790M/C797SConcentration:250nMIncubationTime:24hResult:Significantlysloweddownthehealingrateofscratches.ApoptosisAnalysis[1]CellLine:PC-9EGFR19del/T790M/C797SandPC-9EGFRL858R/T790M/C797SConcentration:500nMIncubationTime:48hResult:significantlyincreasedtheproportionofearlyandlateapoptoticcells體內(nèi)研究EGFR-IN-176(40-80mg/kg,i.g.,oncedailyfor21days)candose-dependentlysignificantlyinhibitorevenpromotetumorregressioninPC-9xenograftmice[1].AnimalModel:Subcutaneouslyinoculatetherightforelimbof6-8-week-oldBALB/c-numicewitha0.2mLsuspensionofPC-9EGFR19del/T790M/C797Scellsataconcentrationof2.5×10^7cells/mLuntilthetumorvolumereaches100-200cubicmillimeters.Dosage:40mg/kg,60mg/kg,80mg/kgAdministration:Oralgavage,oncedailyfor21daysResult:Showedadose-dependenttumorgrowthinhibitoryeffect,thetumorgrowthinhibitionrates(TGI)were80.2%(40mg/kg),92.3%(60mg/kg),and105.7%(80mg/kg),respectively.Observedtumorregressioninthehigh-dosegroup(80mg/kg),thetumorvolumedecreasedtobelowtheinitialvolume.Exhibitedfavorableinvivotolerability,withnomortalityorsignificantbodyweightlossobserved.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESignificantlyinhibitedEGFRphosphorylationandtheactivationofdownstreamsignalingpathways.REFERENCES[1].WuZ,etal.DiscoveryofPotentandSelectivePyrrolo[2,3-d]pyrimidineDerivativesasFourth-GenerationEGFRInhibitorsTargetingTripleMutation.JMedChem.2025Sep25;68(18):19205-19228.McePdfHeightCaution:Prod