Zipalertinib-TAS6417-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZipalertinibCat.No.:HY-112299CASNo.:1661854-97-2Synonyms:TAS6417;CLN-081分?式:C??H??N?O分?量:396.44作?靶點(diǎn):EGFR;Apoptosis作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK;Apoptosis儲存?式:4°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性數(shù)據(jù)體外實驗DMSO:22.73mg/mL(57.34mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5224mL12.6122mL25.2245mL5mM0.5045mL2.5224mL5.0449mL10mM0.2522mL1.2612mL2.5224mL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(protectfromlight,storedundernitrogen)。-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、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%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(5.25mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.25mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(5.25mM);ClearsolutionBIOLOGICALACTIVITY?物活性Zipalertinib(TAS6417;CLN-081)?效的、具有?服活性的、?泛的EGFR突變型的抑制劑，可獨(dú)特的結(jié)合到EGFR鉸鏈區(qū)的ATP結(jié)合位點(diǎn)，其IC50值為1.1-8.0nM。IC50&TargetEGFR1.1-8.0nM(IC50)體外研究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.體內(nèi)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?邊的抑制劑?師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