ASK120067-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEASK120067Cat.No.:HY-138751CASNo.:1934259-00-3分⼦式:C₂₉H₃₂ClN₇O₂分⼦量:546.06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(76.31mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8313mL9.1565mL18.3130mL5mM0.3663mL1.8313mL3.6626mL10mM0.1831mL0.9157mL1.8313mL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%salineSolubility:≥2.5mg/mL(4.58mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.81mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性ASK120067⼀种有效的⼝服活性EGFRT790M抑制剂(IC50:0.3nM)，对EGFRWT(IC50:6.0nM)具有选择性。ASK120067⽤于⾮⼩细胞肺癌(NSCLC)研究的第三代EGFR-TKI。IC50&TargetEGFRT790MEGFRL858R/T790MEGFR(WT)EGFRExon190.5nM(IC50)0.3nM(IC50)6nM(IC50)deletion0.5nM(IC50)体外研究IntheinvitrokinaseassayASK120067potentlyinhibitstheEGFRL858R/T790MandEGFRT790MresistantmutantswithIC50valuesof0.3nMand0.5nM,respectively,aswellastheEGFRexon19delsensitizingmutant(IC50=0.5nM).The50ofASK120067againstwild-typeEGFR(EGFRWT)is6nM[1].ASK120067selectivelyinhibitsthegrowthofEGFR-mutantcelllinesandexhibitspotentantiproliferativeactivityinthemutantEGFRNSCLCcells,withIC50valuesof12nM,6nMand2nMagainstNCI-H1975(T790Mmutation),PC-9,andHCC827cells(sensitizingmutations),respectively.However,itshowsmoderateorweakanti-growthactivitiesinA431,LoVoandA549cells(EGFRWT),withIC50valuesrangingfrom338nMto1541nM[1].ASK120067(0.1-100nM)inhibitsthephosphorylationofEGFRatTyrosineresidue1068anditsdownstreamsignalingproteinsAKTandERKinNCI-H1975cells(EGFRL858R/T790M)evenatlowdosage(0.1-1nM).Additionally,ASK120067inhibitsp-EGFRandp-Aktandp-erkinEGFRWTA431celluntiltheconcentrationreaches10to100nM[1].体内研究ASK120067(oralgavage;5-20mg/kg;oncedaily;21days)resultsinsignificantlyregressedtumorgrowth,withatumorgrowthinhibition(TGI)rateof85.7%,andadministrationof10mg/kgASK120067causesdramatictumorshrinkagewithaTGIrateof99.3%,exhibitingasimilarpotencywithOsimertinib[1].AnimalModel:BALB/cAnudemice[1]Dosage:5-20mg/kgAdministration:Oralgavage;5-20mg/kg;oncedaily;21daysResult:WerewelltoleratedinanimalswithoutobservedbodyweightlossDemonstratedprofoundandselectiveantitumorefficacyanddecreasedTGIrate.SignificantlyinhibitedthephosphorylationofEGFRL858R/T790MandAKTintumortissue.REFERENCES[1].TaoZhang,etal.Discoveryofanovelthird-generationEGFRinhibitorandidentificationofapotentialcombinationstrategytoovercomeresistance.MolCancer.2020May13;19(1):90.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotbeenful