Gefitinib-ZD1839-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGefitinibCat.No.:HY-50895CASNo.:184475-35-2Synonyms:ZD1839分⼦式:C₂₂H₂₄ClFN₄O₃分⼦量:446.9作⽤靶点:EGFR;Autophagy;Apoptosis作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Autophagy;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(279.70mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2376mL11.1882mL22.3764mL5mM0.4475mL2.2376mL4.4753mL10mM0.2238mL1.1188mL2.2376mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：1%DMSO>>99%salineSolubility:0.5mg/mL(1.12mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(4.65mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.65mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.59mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Gefitinib(ZD1839)⼀种有效，选择性和⼝服活性的EGFR酪氨酸激酶抑制剂，IC50为33nM。Gefitinib选择性抑制EGF刺激的肿瘤细胞⽣长(IC50为54nM)，并阻断EGF刺激的肿瘤细胞中EGFR⾃磷酸化。Gefitinib还可诱导细胞⾃噬(autophagy)和凋亡(apoptosis)，可⽤于癌症相关的研究，如肺癌和乳腺癌[1][2][5]。IC50&TargetEGFR体外研究Gefitinib(0.01-0.1ꢀμM,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:5ꢀhResult:InhibitedEGFRtyrosinephosphorylations.CellMigrationAssay[3]CellLine:LLCscell2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEConcentration:0.62μMIncubationTime:72hResult:AbrogatedM2-likemacrophagepromotedinvasionandmigrationofLLCs.体内研究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.户使⽤本产品发表的科研⽂献•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—您⾝边的抑制剂⼤师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