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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemETucatinibhemiethanolateCat.No.:HY-16069ACASNo.:1429755-56-5Synonyms:Irbinitinibhemiethanolate;ARRY-380hemiethanolate;ONT-380hemiethanolate分⼦式:C₂₆H₂₄N₈O₂.₁/₂C₂H₆O分⼦量:503.57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:125mg/mL(248.23mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9858mL9.9291mL19.8582mL5mM0.3972mL1.9858mL3.9716mL10mM0.1986mL0.9929mL1.9858mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.08mg/mL(4.13mM);Clearsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(4.13mM);Clearsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.13mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Tucatinib(Irbinitinib)hemiethanolate有效，具有⼝服活性的、选择性的HER2抑制剂，IC50为8nM。IC50&TargetIC50:8nM(HER2)[1]体外研究TucatinibhemiethanolatehasnanomolaractivityagainstpurifiedHER2enzymeandisapproximately500-foldselectiveforHER2versusEGFRincell-basedassays.TucatinibselectivelyinhibitsthereceptortyrosinekinaseHER2relativetoEGFR[1].TucatinibblocksproliferationandthephosphorylationofHER2anditsdownstreameffector,AktinHER2overexpressingcelllines.IntheEGFRoverexpressingcelllines,itweaklyinhibitsphosphorylationandproliferation,demonstratingthatTucatinibmayhavepotentialtoblockHER2signalingwithoutcausingthetoxicitiesofEGFRinhibition[1].体内研究Tucatinibhemiethanolate(ONT-380hemiethanolate,200mg/kg/d)showsasurvivalbenefitwheneachdrugisdosedatthemaximum-tolerateddose[1].TucatinibanditsactivemetabolitecausesasignificantreductioninbrainpErbB2(80%)[2].Tucatinib(ARRY-380)hemiethanolatedemonstratessignificantdose-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.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•CancerChemotherPharmacol.2021Jun19.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.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.CancerResearch.McePdfHeightCaution:Produ