ASK120067-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEASK120067Cat.No.:HY-138751CASNo.:1934259-00-3分?式:C??H??ClN?O?分?量:546.06作?靶點:EGFR作?通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:41.67mg/mL(76.31mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.8313mL9.1565mL18.3130mL5mM0.3663mL1.8313mL3.6626mL10mM0.1831mL0.9157mL1.8313mL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。-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:≥2.5mg/mL(4.58mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.81mM);ClearsolutionBIOLOGICALACTIVITY?物活性ASK120067?種有效的?服活性EGFRT790M抑制劑(IC50:0.3nM)，對EGFRWT(IC50:6.0nM)具有選擇性。ASK120067?于??細胞肺癌(NSCLC)研究的第三代EGFR-TKI。IC50&TargetEGFRT790MEGFRL858R/T790MEGFR(WT)EGFRExon190.5nM(IC50)0.3nM(IC50)6nM(IC50)deletion0.5nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenful