XL228-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEXL228Cat.No.:HY-15749CASNo.:898280-07-4分⼦式:C₂₂H₃₁N₉O分⼦量:437.54作⽤靶点:AuroraKinase;Bcr-Abl;IGF-1R;Src作⽤通路:CellCycle/DNADamage;Epigenetics;ProteinTyrosineKinase/RTK储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥83.33mg/mL(190.45mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2855mL11.4275mL22.8551mL5mM0.4571mL2.2855mL4.5710mL10mM0.2286mL1.1428mL2.2855mL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(4.75mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.75mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.75mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性XL228多靶点的酪氨酸激酶抑制剂，对Bcr-Abl，AuroraA，IGF-1R，Src和Lyn的IC50值分别为5，3.1，1.6，6.1，2nM。IC50&TargetAuroraAIGF-1R3.1nM(IC50)1.6nM(IC50)体外研究XL228showsabroadpatternofproteinkinaseinhibition,includingthetyrosinekinasesIGF1R,SRC,ABL,FGFR1-3,andALKandtheserine/threoninekinasesAuroraAandAuroraB.ApanelofkinaseinhibitorsincludingXL228isprofiledagainstaseriesofcancercelllineswithknownalterationsinmajorsignalingpathways.Approximately30%ofthelinesdemonstrateXL228IC50valuesof[2].ItdisplayslownanomolarbiochemicalactivityagainstwildtypeAblkinase(Ki=5nM),aswellastheT315IformofAblresistanttoimatinibanddasatinib(Ki=1.4nM).XL228inhibitsphosphorylationofBCR-ABLanditssubstrateSTAT5inK562cellsinvitrowithIC50sof33and43nM,respectively[3].体内研究Single-dosepharmacodynamicsstudiesdemonstrateapotenteffectofXL228onBCR-ABLsignalinginK562xenografttumors.PhosphorylationofBCR-ABLisdecreasedby50%atXL228plasmaconcentrationsof3.5μM;asimilardecreaseinphospho-STAT5occurredat0.8μMplasmaconcentration[3].户使⽤本产品发表的科研⽂献•Science.2017Dec1;358(6367):eaan4368.•NatBiomedEng.2018Aug;2(8):578-588.•TechnicalUniversityofMunich.24.01.2018.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CortesJ,etal.PreliminaryClinicalActivityinaPhaseITrialoftheBCR-ABL/IGF-1R/AuroraKinaseInhibitorXL228inPatientswith

Ph++LeukemiaswithEitherFailuretoMultipleTKITherapiesorwithT315IMutation.Blood2008112:3232[2].DouglasO,etal.AbstractC192:CharacterizationofthetargetprofileofXL228,amulti‐targetedproteinkinaseinhibitorinphase1clinicaldevelopment.MolCancerTher2009;8(12Suppl):C192.[3].ShahN,etal.TargetingDrug-ResistantCMLandPh+-ALLwiththeSpectrumSelectiveProteinKinaseInhibitorXL228.Blood20072/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE110:474;McePdfHeightCaution:Producthasnotbeenfully