Mobocertinib-succinate-TAK-788-succinate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEMobocertinibsuccinateCat.No.:HY-135815ACASNo.:2389149-74-8Synonyms:TAK-788succinate;AP32788succinate分⼦式:C₃₆H₄₅N₇O₈分⼦量:703.78作⽤靶点:EGFR作⽤通路:JAK/STATSignaling;ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:125mg/mL(177.61mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.4209mL7.1045mL14.2090mL5mM0.2842mL1.4209mL2.8418mL10mM0.1421mL0.7104mL1.4209mL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(sealedstorage,awayfrommoisture)。-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>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.96mM);Clearsolution1/4MasterofBioactiveMolecules—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(2.96mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Mobocertinib(TAK-788)succinate⼀种⼝服有效并且不可逆的EGFR/HER2抑制剂。Mobocertinibsuccinate能选择性地(相较于野⽣型EGFR)抑制含有EGFRex20ins的致癌突变体。Mobocertinibsuccinate可⽤于NSCLC的研究。IC50&TargetEGFRexon20insertionHER2EGFR(WT)体外研究Mobocertinibsuccinate(1.5nM-10μM;7days)inhibitsLU0387(NPH)cellswithIC50of21nM[1].Mobocertinibsuccinate(2h)potentlyinhibitsEGFRwithcommonactivatingmutations(HCC827(D),HCC4011(L))orwithaT790Mmutation(H1975(LT))morepotentlythanWTEGFR(A431(WT))[1].Mobocertinibsuccinate(0.1nM-1μM;6h)inhibitspEGFRandpERK1/2inCUTO14(ASV)cells[1].Mobocertinibsuccinate(0.3nM-1μM;6h)inhibitsEGFRanddownstreamsignaling[1].Mobocertinibsuccinate(0.01,0.1and1μM;6h)inhibitsHER2signalinginH1781(HER2Exon20G776>VC),Ba/F3(HER2exon20YVMA)cells[2].CellViabilityAssay[1]CellLine:LU0387(NPH)cellsConcentration:1.5nM-10μMIncubationTime:7daysResult:ShowedgoodinhibitionactivityforLU0387(NPH)cellswithIC50of21nM.CellViabilityAssay[1]CellLine:A431(WT),HCC827(D),HCC4011(L),H1975(LT)cellsConcentration:IncubationTime:2hResult:InhibitedEGFRwithcommonactivatingmutationsofHCC827(D),HCC4011(L)cellsandT790MmutationofH1975(LT)withIC50sof4,1.3and9.8nMrespectively,whichmorepotentlythanWTEGFR(A431(WT);IC50of35nM).WesternBlotAnalysis[1]CellLine:CUTO14(ASV)cellsConcentration:0.1nM-1μM2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEIncubationTime:6hResult:RobustlyinhibitedEGFRsignaling,reaching80%and100%inhibitionofphosphorylatedEGFR(pEGFR)atconcentrationsof100nMand1μM,respectively.WesternBlotAnalysis[1]CellLine:HCC827(D),HCC4011(L),H1975(LT)cellsConcentration:0.3nM-1μMIncubationTime:6hResult:PotentlyinhibitedEGFRanddownstreamsignalinginHCC827(D),HCC4011(L)andH1975(LT)cells.WesternBlotAnalysis[2]CellLine:H1781(HER2Exon20G776>VC),Ba/F3(HER2exon20YVMA)cellsConcentration:0.01,0.1and1μMIncubationTime:6hResult:InhibitedHER2signalinginH1781andBa/F3-HER2exon20YVMAmutantcellsat0.1μMwithsignificantlydecreasedphosphorylationsofHER2,AKT,andERK1/2inadose-dependentmanner.体内研究Mobocertinibsuccinate(3,10,30mg/kg;p.o.;oncedailyfor20days)significantlyinducestumorgrowthinhibition[1].AnimalModel:FemaleAthymicNude-Foxn1numice(humanNSCLCH1975LTtumormodel)[1].Dosage:3,10,30mg/kgAdministration:Oral;oncedailyfor20days.Result:Decreasedthemeantumorvolumeby44%and92%whenat3mg/kgand10mg/kg,respectively,relativetothetumorsizeofvehiclegroup.Induceda76%tumorregressionrelativetothepretreatmenttumorsizeat30mg/kg.户使⽤本产品发表的科研⽂献•Cells.2021,10(12),3561.•MolPharm.2022Oct21.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].GonzalvezF,etal.Mobocertinib(TAK-788):ATargetedInhibitorofEGFRExon20InsertionMutantsinNon-SmallCellLungCancer.CancerDiscov.2021Jul;11(7):1672-1687.[2].anH,etal.TargetingHER2Exon20Insertion-MutantLungAdenocarcinomawithaNovelTyrosineKinaseInhibitorMobocertinib.CancerRes.2021Oct15;8