Zipalertinib-TAS6417-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEZipalertinibCat.No.:HY-112299CASNo.:1661854-97-2Synonyms:TAS6417;CLN-081分⼦式:C₂₃H₂₀N₆O分⼦量:396.44作⽤靶点:EGFR;Apoptosis作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Apoptosis储存⽅式:4°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性数据体外实验DMSO:22.73mg/mL(57.34mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5224mL12.6122mL25.2245mL5mM0.5045mL2.5224mL5.0449mL10mM0.2522mL1.2612mL2.5224mL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(protectfromlight,storedundernitrogen)。-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%salineSolubility:≥2.08mg/mL(5.25mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.25mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Zipalertinib(TAS6417;CLN-081)⾼效的、具有⼝服活性的、⼴泛的EGFR突变型的抑制剂，可独特的结合到EGFR铰链区的ATP结合位点，其IC50值为1.1-8.0nM。IC50&TargetEGFR1.1-8.0nM(IC50)体外研究Zipalertinib(TAS6417)inhibitsEGFRphosphorylationanddownstreammoleculesinNSCLCcelllinesexpressingEGFRexon20insertions,resultingincaspaseactivation[1].Zipalertinib(TAS6417)isarobustinhibitoragainstthemostcommonEGFRmutations(exon19deletionsandL858R)andthemostpotentagainstcellsharboringEGFR-T790M(1st/2ndgenerationTKIresistancemutation)[2].Zipalertinib(TAS6417)covalentlymodifiedthecysteineresidueatposition797ofrecombinantEGFRharboringanin-frameinsertionmutationintheexon20region[1].Zipalertinib(TAS6417)inhibitsEGFRsignaltransduction,leadingtocellgrowthinhibitionandapoptosisinductioninNSCLCcellsdrivenbyEGFRexon20insertionmutations[1].Zipalertinib(TAS6417)(0-10μM)inhibitscellproliferationandEGFRsignalinginNSCLCcelllinesharboringEGFRcommonmutationsinthepresenceorabsenceofT790M[2].ApoptosisAnalysis[2]CellLine:PC-9,H1975,BID007,BID019,BEAS-2Bcells.Concentration:0-10μM.IncubationTime:24-48h.Result:LedtoapoptosisviainhibitionofmutantEGFR.体内研究Zipalertinib(TAS6417)(10-200mg/kg)causespersistenttumorregressioninvivoinEGFRexon20insertion-driventumormodels.TAS6417inhibitsmutantEGFRintumorsbutnotWTEGFRinskintissues[1].Zipalertinib(TAS6417)hadnoeffectonEGFR-independentproliferationinNCI-H23orNCI-H460cells[1].Zipalertinib(TAS6417)administeredat20mg/kg,whichachievescompletesuppressionoftumorgrowth,inducesasignificantdecreaseinpEGFR,leadingtoreductionofpAKTandpERKat1h.Theinhibitoryeffectisstillnotedat6h,andphosphorylationofEGFR,ATK,andERKrecoveredby24h[1].Zipalertinib(TAS6417)(100and200mg/kg/day)prolongssurvivalofanimalsbearinglungcancer[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:MiceimplantedwithNCI-H1975EGFRD770_N771insSVDxenografts[1].Dosage:50and100mg/kg.Administration:Orallyoncedailyfor14days.Result:Showedmarkedtumorgrowthinhibitionwithtreatment/control(T/C)ratiosof51%and19%,respectively.REFERENCES[1].HasakoS,etal.TAS6417,ANovelEGFRInhibitorTargetingExon20InsertionMutations.MolCancerTher.2018Aug;17(8):1648-1658.[2].HibikiUdagawa,etal.TAS6417/CLN-081IsaPan-Mutation-SelectiveEGFRTyrosineKinaseInhibitorwithaBroadSpectrumofPreclinicalActivityagainstClinicallyRelevantEGFRMutations.MolCancerRes.2019Nov;17(11):2233-2243.McePdfHeig