Canertinib-CI-1033-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECanertinibCat.No.:HY-10367CASNo.:267243-28-7Synonyms:CI-1033;PD-183805分?式:C??H??ClFN?O?分?量:485.94作?靶點:EGFR;Orthopoxvirus作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗Ethanol:12.5mg/mL(25.72mM;Needultrasonic)DMSO:4.9mg/mL(10.08mM;Needwarming)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0579mL10.2893mL20.5787mL5mM0.4116mL2.0579mL4.1157mL10mM0.2058mL1.0289mL2.0579mL請根據(jù)產(chǎn)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(fù)凍融造成的產(chǎn)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(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(xiàn)沉淀1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%EtOH>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.57mM);Clearsolution2.請依序添加每種溶劑：10%EtOH>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(2.57mM);Clearsolution3.請依序添加每種溶劑：10%EtOH>>90%cornoilSolubility:≥1.25mg/mL(2.57mM);ClearsolutionBIOLOGICALACTIVITY?物活性Canertinib(CI-1033;PD-183805)有效的，不可逆的EGFR抑制劑；抑制細胞EGFR和ErbB2??磷酸化的IC50值分別為7.4和9nM。Canertinib可以?于研究??的?痘病毒呼吸道感染。IC50&TargetEGFRErbB27.4nM(IC50)9nM(IC50)體外研究Canertinibsignificantlyinhibitsgrowthofculturedmelanomacells,RaH3andRaH5,inadose-dependentmanner.IC50isapproximately0.8μMandby5μMbothcelllinesarecompletelygrowth-arrestedwithin72hoftreatment.IncubationofexponentiallygrowingRaH3andRaH5with1μMcanertinibaccumulatedthecellsintheG1-phaseofthecellcyclewithin24hoftreatmentwithoutinductionofapoptosis.1μMcanertinibinhibitsErbB1-3receptorphosphorylationwithaconcomitantdecreaseofAkt-,Erk1/2-andStat3activityinbothcelllines[2].Canertinibalsoisapotentactivatorofexosomesecretion[3].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻?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