PD153035-SU-5271-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEPD153035Cat.No.:HY-14346CASNo.:153436-54-5Synonyms:SU-5271;AG1517;ZM252868分⼦式:C₁₆H₁₄BrN₃O₂分⼦量:360.21作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:33.33mg/mL(92.53mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7762mL13.8808mL27.7616mL5mM0.5552mL2.7762mL5.5523mL10mM0.2776mL1.3881mL2.7762mL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.请依序添加每种溶剂：10%DMSO>>90%cornoil1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.94mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性PD153035(SU-5271;AG1517;ZM252868)有效地EGFR抑制剂，Ki和IC50值分别为6和25pM。IC50&TargetEGFREGFR6pM(Ki)25pM(IC50)体外研究PD153035(SU5271)inhibitsEGF-stimulatedreceptorautophosphorylationinA431humanepidermoidcarcinomacells,withanIC50of14nM[1].PD153035(SU5271)haslittleeffectonPDGFR,FGFR,CSF-1receptor,theinsulinreceptor,oronsrctyrosinekinasesatconcentrationsashighas50μM.PD153035(SU5271)rapidlysuppressesautophosphorylationoftheEGFreceptoratlownanomolarconcentrationsinfibroblastsorinhumanepidermoidcarcinomacellsandselectivelyblocksEGF-mediatedcellularprocessesincludingmitogenesis,earlygeneexpression,andoncogenictransformation[2].PD153035(SU5271)causesadose-dependentgrowthinhibitionofEGFreceptor-positivecelllines,beginningatlessthanmicromolarconcentrations,andtheIC50islessthan1pMinmostcases[3].体内研究PD153035(SU5271)levelsintheplasmaandtumorriseto50and22μMwithin15minutesfollowingasinglei.p.doseof80mg/kg.WhiletheplasmalevelsofPD153035(SU5271)fallsbelow1μMby3hours,inthetumorsitremainsatmicromolarconcentrationsforatleast12hours.ThetyrosinephosphorylationoftheEGFreceptorisrapidlysuppressedby80-90%inthetumors[4].PROTOCOLCellAssay[3]DifferentEGFreceptor-overexpressingcelllines(A431,Difi,MDA-MB-468,MDA-MB-231,DU145,SiHa,C4i,andMEl80)aretreatedwithPD153035atincreasingconcentrationsof0.125-2.5p.M.Growthinhibitoryeffectinmonolayercellcultureisassessed[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:MiceareinjectedwithPD153035(SU5271)(80mg/kg)orvehicleandrumorsareexcisedat20Administration[3]minutesand180minutesandextractsareprepared.Twomiceareusedforeachtimepointandtheexperimentisrepeatedfourtimes.WithineachofthefourexperimentsANOVAisusedtocomparetheinhibitionbyPD153035(SU5271)oftheEGF-stimulation[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2018Jun5;9(1):2174.•CellDeathDis.2022Jul25;13(7):647.•Elife.2015Feb10;4:e05178.•IntJStemCells.2022Jun30.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•GenCompEndocrinol.2020Dec1;299:113616.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BridgesAJ,etal.Tyrosinekinaseinhibitors.8.Anunusuallysteepstructure-activityrelationshipforanaloguesof4-(3-bromoanilino)-6,7-dimethoxyquinazoline(PD153035),apotentinhibitoroftheepidermalgrowthfactorreceptor.JMedChem.1996Jan[2].FryDW,etal.Aspecificinhibitoroftheepidermalgrowthfactorreceptortyrosinekinase.Science.1994Aug19;265(5175):1093-5.[3].BosM,etal.PD153035,atyrosinekinaseinhibitor,preventsepidermalgrowthfactorreceptoractivationandinhibitsgrowthofcancercellsinareceptornumber-dependentmanner.ClinCancerRes.1997Nov;3(11):2099-106.[4].KunkelMW,etal.InhibitionoftheepidermalgrowthfactorreceptortyrosinekinasebyPD153035inhumanA431tumorsinathymicnudemice.InvestNewDrugs.1996;13(4):295-