Canertinib-CI-1033-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECanertinibCat.No.:HY-10367CASNo.:267243-28-7Synonyms:CI-1033;PD-183805分⼦式:C₂₄H₂₅ClFN₅O₃分⼦量:485.94作⽤靶点:EGFR;Orthopoxvirus作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验Ethanol:12.5mg/mL(25.72mM;Needultrasonic)DMSO:4.9mg/mL(10.08mM;Needwarming)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0579mL10.2893mL20.5787mL5mM0.4116mL2.0579mL4.1157mL10mM0.2058mL1.0289mL2.0579mL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1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE、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%EtOH>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.57mM);Clearsolution2.请依序添加每种溶剂：10%EtOH>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(2.57mM);Clearsolution3.请依序添加每种溶剂：10%EtOH>>90%cornoilSolubility:≥1.25mg/mL(2.57mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Canertinib(CI-1033;PD-183805)有效的，不可逆的EGFR抑制剂；抑制细胞EGFR和ErbB2⾃⾝磷酸化的IC50值分别为7.4和9nM。Canertinib可以⽤于研究⼩⿏的⽜痘病毒呼吸道感染。IC50&TargetEGFRErbB27.4nM(IC50)9nM(IC50)体外研究Canertinibsignificantlyinhibitsgrowthofculturedmelanomacells,RaH3andRaH5,inadose-dependentmanner.IC50isapproximately0.8μMandby5μMbothcelllinesarecompletelygrowth-arrestedwithin72hoftreatment.IncubationofexponentiallygrowingRaH3andRaH5with1μMcanertinibaccumulatedthecellsintheG1-phaseofthecellcyclewithin24hoftreatmentwithoutinductionofapoptosis.1μMcanertinibinhibitsErbB1-3receptorphosphorylationwithaconcomitantdecreaseofAkt-,Erk1/2-andStat3activityinbothcelllines[2].Canertinibalsoisapotentactivatorofexosomesecretion[3].体内研究Canertinibshowssuperiorinvivoantitumoractivity,givinggrowthdelaysinA431xenograftsexceeding50daysfollowingoraladministration[1].Thegrowthofhumanmalignantmelanomaxenografts,RaH3andRaH5,innudemiceissignificantlyinhibitedbyi.p.injectionsof40mg/kg/daycanertinib(Fig.4).Theanti-proliferativeeffectonmelanomaxenograftsisvisiblealreadywithin4daysoftreatmentandfurtherincreasedthroughoutthetreatmentperiodasobservedthroughthedifferencesintumorvolumes,reachingstatisticalsignificancewithin18daysoftreatment[2].PROTOCOLKinaseAssay[1]EnzymeassaysforIC50determinationsareperformedin96-wellfilterplates.Thetotalvolumeis0.1mLcontaining20mMHepes,pH7.4,50mMsodiumvanadate,40mMmagnesiumchloride,10µMadenosinetriphosphate(ATP)containing0.5mCiof[32P]ATP,20mgofpolyglutamicacid/tyrosine,10ngofEGFRtyrosinekinase,andappropriatedilutionsofinhibitor(Canertinib).AllcomponentsexcepttheATPareaddedtothewellandtheplateisincubatedwithshakingfor10minat25°C.Thereactionisstartedbyadding[32P]ATP,andtheplateisincubatedat25°Cfor10min.Thereactionisterminatedbyadditionof0.1mLof20%trichloroaceticacid(TCA).Theplateiskeptat4°Cforatleast15mintoallowthesubstratetoprecipitate.Thewellsisthenwashedfivetimeswith0.2mLof10%TCAand32Pincorporationdeterminedwithaplatecounter[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[2]RaH3andRaH5cellsaretreatedwithincreasingconcentrations(0-10μM)ofCanertinibfor72h.Thecellsaresuspendedinbufferandcounted[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:Canertinibtreatmentstartswhenthetumorsshowreliablegrowth.ThemicearerandomizedintoAdministration[2]controlandtreatmentgroups.InthecanertinibtreatedRaH3group(n=4)andRaH5group(n=7)eachmousereceivesi.p.injectionsof1.2mgcanertinib(40mg/kg/day)in0.1ml0.15MNaCl5daysaweek.ThecontrolRaH3(n=3)andRaH5(n=7)micereceivei.p.injectionsofvehicleonlyaccordingtothesameregimen.Attheendofthetreatmentperiod,themicearesacrificedbycervicaldislocationwhereafterthetumorsareremovedandweighed[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•JMedChem.2019May9;62(9):4772-4778.•JBiolChem.2012Mar23;287(13):9742-52.•JCellSci.2015Sep1;128(17):3317-29.•Biochemistry.2018Feb27;57(8):1369-1379.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SmeeDF,et,al.Progressinthediscoveryofcompoundsinhibitingorthopoxvirusesinanimalmodels.AntivirChemChemother.2008;19(3):115-24.[2].SmaillJB,etal.Tyrosinekinaseinhibitors.17.Irreversibleinhibitorsoftheepidermalgrowthfactorreceptor:4-(phenylamino)quinazoline-and4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamidesbearingadditionalsolubilizingfunctions.JMedChem.[3].DjerfSeverinssonEA,etal.Thepan-ErbBreceptortyrosinekinaseinhibitorcanertinibpromotesapoptosisofmalignantmelanomainvitroanddisplaysanti-tumoractivityinvivo.BiochemBiophysResCommun.2011Oct28;414(3):563-8.[4].McAndrewsKM,et,al.Mechanismsassociat