EGFR-IN-44-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEGFR-IN-44Cat.No.:HY-145844分?式:C??H??ClN?O?S分?量:537.08作?靶點:EGFR;Apoptosis作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Apoptosis儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性EGFR-IN-44(Compound6a)?種有效的、具有?服活性的EGFRtyrosinekinase抑制劑，其IC50值為4.11nM。EGFR-IN-44誘導(dǎo)細(xì)胞凋亡(apoptosis)，?服?物利?度為33.57%。EGFR-IN-44可以?于??細(xì)胞肺癌的研究[1]。IC50&TargetIC50:0.26nM(EGFRT790M/L858R),1.33nM(EGFRL858R),4.11nM(EGFR)[1]體外研究EGFR-IN-44(Compound6a)(0-10μM,72h)showsanti-proliferativeactivitiesagainsttumorcelllines[1].EGFR-IN-44bindstotheATPbindingsiteofEGFR[1].EGFR-IN-44(0-10nM,48h)inducesH1975cellapoptosisviathemitochondrialpathway,arrestscellcycleinG0/G1phase,andsuppressescellmigration[1].EGFR-IN-44(0-10nM,48and72h)showshypotoxicityagainstnormalcells[1].CellProliferationAssay[1]CellLine:H1975(EGFRT790M/L858R),PC9(EGFRdel19),andH292(EGFRWT)Concentration:0-10μMIncubationTime:72hResult:Showedanti-proliferativeactivitieswithIC50valuesof0.0022±0.001,0.0048±0.001,and4.499±0.057μMagainstH1975,PC9,andH292cells,respectively.ApoptosisAnalysis[1]1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellLine:H1975Concentration:1,5,and10nMIncubationTime:48hResult:Effectivelyinducedcellapoptosisinadose-dependentmanner.Resultedin33.7%,52.4%,and56.2%apoptosisat1,5,and10μM,respectively,comparedto5.81%apoptosisinthecontrolgroup.WesternBlotAnalysis[1]CellLine:H1975Concentration:5,10,and25nMIncubationTime:48hand72hResult:Dose-dependentlyupregulatedtheexpressionlevelsoftheproapoptoticproteinsBadandBaxanddownregulatedtheexpressionleveloftheantiapoptoticproteinBcl-2.SufficientlyreducedthephosphorylationofEGFRandAKT.CellCycleAnalysis[1]CellLine:H1975Concentration:5nMIncubationTime:0,12,24,or48hResult:ExhibitedasignificantincreaseintheG0/G1cellpopulationandadramaticdecreaseinG2/Mphase.CellCytotoxicityAssay[1]CellLine:LO2,HK2,HLF,and293AConcentration:0.1,1,5,and10μMIncubationTime:48hand72hResult:ShowedhypotoxicitywithIC50valuesof7.247,4.586,3.787,and2.925μMagainstLO2,HK2,HLF,and293Acells,respectively.Thecellmorphologywaschangedcomparedtothecontrol.體內(nèi)研究EGFR-IN-44(Compound6a)(25mg/kg;i.g.;daily,7days)showsstrongantitumoractivitywithoutobvioustoxicity[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:MaleBALB/cnudemice(5weeksold,18-20g),H1975xenograftmodel[1]Dosage:25mg/kgAdministration:Intragastricadministration,daily,7daysResult:Showedstrongtumorinhibition(TGI=90.24%)withoutobvioustoxicity.AnimalModel:MaleSprague–Dawley(SD)rats[1]Dosage:1mg/kgand5mg/kgAdministration:Intravenousinjectionandoraladministration(PharmacokineticAnalysis)Result:InVivoPKparametersofEGFR-IN-44[1]ParametersDose(mg/kg)EGFR-IN-445(po)1(iv)t1/2(h)8.60±1.81.42±0.1Tmax(h)4.00±0.002/Cmax(ng/mL)80.40±2.7/VzF_pred(L/kg)220.80±41.26.83±08AUC0-t(H.ng/mL)490.41±29.9291.91±38.2AUC0-∞(H.ng/mL)491.02±44.2295.76±38.8MRT0-last(h)7.93±0.81.35±01CL(mL/h/kg)17.79±3.93.12±0.4F(%)33.57±5.9/F=(AUC0-inf-PO×DOSEIV)/(AUC0-inf-IV×DOSEPO)*100%.REFERENCES[1].BaijiaoAn,etal.Novelthird-generationpyrimidines-basedEGFRtyrosinekinaseinhibitorstargetingEGFRT790Mmutationinadvancednon-smallcelllungcancer.BioorgChem.2022May;122:105743.McePdfHeightCaution:Produ