Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGefitinibCat.No.:HY-50895CASNo.:184475-35-2Synonyms:ZD1839分?式:C??H??ClFN?O?分?量:446.9作?靶點:EGFR;Autophagy;Apoptosis作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Autophagy;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:125mg/mL(279.70mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2376mL11.1882mL22.3764mL5mM0.4475mL2.2376mL4.4753mL10mM0.2238mL1.1188mL2.2376mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的?式助溶)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：1%DMSO>>99%salineSolubility:0.5mg/mL(1.12mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.65mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.65mM);Clearsolution4.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.59mM);ClearsolutionBIOLOGICALACTIVITY?物活性Gefitinib(ZD1839)?種有效，選擇性和?服活性的EGFR酪氨酸激酶抑制劑，IC50為33nM。Gefitinib選擇性抑制EGF刺激的腫瘤細胞?長(IC50為54nM)，并阻斷EGF刺激的腫瘤細胞中EGFR?磷酸化。Gefitinib還可誘導細胞?噬(autophagy)和凋亡(apoptosis)，可?于癌癥相關的研究，如肺癌和乳腺癌[1][2][5]。IC50&TargetEGFR體外研究Gefitinib(0.01-0.1?μM,72h)resultsinincreasedphosphotyrosineloadofthereceptor,increasedsignallingtoERKandstimulationofproliferationandanchorage-independentgrowth[2].Gefitinib(1-2μM,72h)significantlydecreasesEGFRvIIIphosphotyrosineload,EGFRvIII-mediatedproliferationandanchorage-independentgrowth[2].Gefitinib(0.62μM,24-72h)inhibitsIL-13-inducedM2-likepolarizationofRAW264.7cellsthroughtheSTAT6-dependentsignalingpathway[3].Gefitinib(0.62μM,72h)inhibitsM2-likemacrophage-promotedinvasionandmigration[3].Gefitinib(0-10μM,72h)inducesapoptosis(inductionofBIMprotein)inNSCLCCellLines(H3255andHCC827cells)[4].Gefitinib(100nM,24h)suppressesmacropinocytosisandincreasesthecellularuptakeofextracellularvesicles(EVs)inHCC827andA549cells[6].Gefitinib(1.5-60μM,48h)increasesinhibitionofproliferationinH358RandA549Rcells(Cisplatin-resistantwtEGFRNSCLCcelllines)[7].WesternBlotAnalysis[2]CellLine:NR6wtEGFR,NR6WandNR6MConcentration:1,10,100μMIncubationTime:5?hResult:InhibitedEGFRtyrosinephosphorylations.CellMigrationAssay[3]CellLine:LLCscell2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0.62μMIncubationTime:72hResult:AbrogatedM2-likemacrophagepromotedinvasionandmigrationofLLCs.體內研究Gefitinib(Oraladministration,75mg/kg/d,21days)inhibitstheM2-likepolarizationofmacrophagesinLLCmicemetastasismodel[3].Gefitinib(Oraladministration,75mg/kgfortheinitialweek,dailyfor5consecutivedaysperweek)eliminatesphosphorylationofHER2andHER3andsignalingthroughMAPKandAktinlobularhyperplasiasandcarcinomas,increasesMAPKactivityandcytokineproductioninsplenocytesandlymphnodes[5].Gefitinib(Oralgavage,150mg/kg,daily)enhancestheanti-tumoreffectofCisplatininH358Rxenograft[7].AnimalModel:LLCmicemetastasismodel[3]Dosage:75mg/kg/d,for21days.Administration:OraladministrationResult:Reducedthenumberoflungmetastasisnodules,down-regulatedtheexpressionofM2markergenesandthepercentagesCD206+andCD68+macrophagesintumortissues.AnimalModel:BALB-NeuTtransgenicmousemodel[5]Dosage:75mg/kgfortheinitialweek,andincreasedby15mg/kgeveryotherweek,dailyfor5consecutivedaysperweek,followedby2dayswithouttreatmentandrepeatedfor8–9weeks.Administration:OraladministrationResult:Reducedtumormultiplicityfrom9.6to0.58(83%),andreducedthenumberandsizeoflobulesandlobularnodulesintreatedmice.戶使?本產品發表的科研?獻?CellRes.2021Jun;31(6):631-648.?CellRes.2020Oct;30(10):833-853.?CancerCell.2018Jun11;33(6):1061-1077.e6.?SignalTransductTargetTher.2019Dec13;4:60.?NatBiomedEng.2018Aug;2(8):578-588.Seemorecustomervalidationsonwww.MedChemEREFERENCES3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].PedersenMW,etal.DifferentialresponsetogefitinibofcellsexpressingnormalEGFRandthemutantEGFRvIII.BrJCancer.2005Oct17;93(8):915-23.[2].MuhammadTariq,etal.GefitinibinhibitsM2-likepolarizationoftumor-associatedmacrophagesinLewislungcancerbytargetingtheSTAT6signalingpathway.ActaPharmacolSin.2017Nov;38(11):1501-1511.[3].MarkSCragg,etal.Gefitinib-inducedkillingofNSCLCcelllinesexpressingmutantEGFRrequiresBIMandcanbeenhancedbyBH3mimetics.PLoSMed.2007Oct;4(10):1681-89;discussion1690.[4].MariePPiechocki,etal.GefitinibpreventscancerprogressioninmiceexpressingtheactivatedratHER2/neu.IntJCancer.2008Apr15;122(8):1722-9.[5].TomoyaTakenaka,etal.EffectsofgefitinibtreatmentoncellularuptakeofextracellularvesiclesinEGFR-mutantnon-smallcelllungcancercells.IntJPharm.2019Dec15;572:118762.[6].AminLi,etal.Gefitinibsensitizationofcisplatin-resistantwild-typeEGFRnon-smallcelllungcancercells.JCancerResClinOncol.2020Jul;146(7):1737-1749.[7].WakelingAE,etal.ZD1839:anorallyactiveinhibitorofepidermalgrowthfactorsigna