Tucatinib-Irbinitinib-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETucatinibCat.No.:HY-16069CASNo.:937263-43-9Synonyms:Irbinitinib;ARRY-380;ONT-380分⼦式:C₂₆H₂₄N₈O₂分⼦量:480.52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:41.67mg/mL(86.72mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0811mL10.4054mL20.8108mL5mM0.4162mL2.0811mL4.1622mL10mM0.2081mL1.0405mL2.0811mL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>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:2.08mg/mL(4.33mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.33mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.33mM);Clearsolution4.请依序添加每种溶剂：30%SBE-β-CDSolubility:10mg/mL(20.81mM);Suspensionsolution;Needultrasonic5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.62mg/mL(5.45mM);Clearsolution6.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.62mg/mL(5.45mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tucatinib(Irbinitinib)有效，具有⼝服活性的、选择性的HER2抑制剂，IC50为8nM。IC50&TargetHER2体外研究TucatinibhasnanomolaractivityagainstpurifiedHER2enzymeandisapproximately500-foldselectiveforHER2versusEGFRincell-basedassays.TucatinibselectivelyinhibitsthereceptortyrosinekinaseHER2relativetoEGFR[1].TucatinibblocksproliferationandthephosphorylationofHER2anditsdownstreameffector,AktinHER2overexpressingcelllines.IntheEGFRoverexpressingcelllines,itweaklyinhibitsphosphorylationandproliferation,demonstratingthatTucatinibmayhavepotentialtoblockHER2signalingwithoutcausingthetoxicitiesofEGFRinhibition[1].体内研究Tucatinib(ONT-380,200mg/kg/d)showsasurvivalbenefitwheneachdrugisdosedatthemaximum-tolerateddose[1].TucatinibanditsactivemetabolitecausesasignificantreductioninbrainpErbB2(80%)[2].Tucatinib(ARRY-380)demonstratessignificantdose-relatedtumorgrowthinhibition(TGI;50%at50mg/kg/dand96%at100mg/kg/d)withnumerouspartialregressions(>50%reductionfrombaselinesize)atthehigherdoselevelin9/12animals.Tucatinib(50mg/kg/d)incombinationwithtrastuzumabshowsa98%TGIwithcompleteregressionsin9/12animalsandtwopartialregressions[3].AnimalModel:Femalenudemice[3].Dosage:200mg/kg/d.Administration:PO,daily.Result:Exhibitedanti-tumoractivityandbenefitedsurvival.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•CancerDiscov.2021Dec15;candisc.1265.2020.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•ActaPharmacolSin.2022Feb28.•CancerChemotherPharmacol.2021Oct;88(4):633-642.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Moulder-ThompsonS,etal.Phase1StudyofONT-380,aHER2Inhibitor,inPatientswithHER2+AdvancedSolidTumors,withanExpansionCohortinHER2+MetastaticBreastCancer(MBC).ClinCancerRes.2017Jan4.pii:clincanres.1496.2016.[2].Abstract:In:Proceedingsofthe103rdAnnualMeetingoftheAmericanAssociationforCancerResearch;2012Mar31-Apr4;Chicago,IL.Philadelphia(PA):AACR;CancerRes2012;72(8Suppl):Abstractnr852.doi:1538-7445.AM2012-852[3].P.Lee,etal.InVivoActivityofARRY-380,aPotent,SmallMoleculeInhibitorofErbB2inCombinationwithRP-56976.CancerResearchMcePdfHeight