EN6-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEN6Cat.No.:HY-128892CASNo.:1808714-73-9分⼦式:C₁₉H₁₄F₂N₄O₂分⼦量:368.34作⽤靶点:Autophagy作⽤通路:Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:5mg/mL(13.57mM;Needultrasonic)Ethanol:1.11mg/mL(3.01mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7149mL13.5744mL27.1488mL5mM0.5430mL2.7149mL5.4298mL10mM0.2715mL1.3574mL2.7149mL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：50%PEG300>>50%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:10mg/mL(27.15mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性EN6⼀种⼩分⼦体内⾃噬(autophagy)激活剂，其共价靶向溶酶体v-ATP酶的ATP6V1A亚中的半胱氨酸277。EN6介导的ATP6V1A修饰使v-ATP酶与Rag解偶联，导致mTORC1信号的抑制，增加溶酶体酸化，并激活⾃噬。EN6还能以溶酶体依赖的⽅式除TDP-43聚集物(额颞叶痴呆的致病因⼦)。体外研究EN6(50μM;1,4,8h)increasesthelevelsofLC3BII,andtriggersformationofLC3punctainatime-anddose-dependentmanner,inHEK293Acells[1].EN6leadstosignificantincreasesinthenumberautophagosomesandautolysosomesinHEK293Acells[1].EN6(25μM;1h)blocksmTORC1lysosomallocalizationandactivationinHEK293Acells[1].EN6(50μM;4h)activatesthev-ATPaseandlysosomeacidificationinHEK293Acells[1].EN6(25μM;7h)promotesautophagicclearanceofproteinaggregatesinIPTG-inducibleGFP-TDP43U2OSosteosarcomacelllinemodel[1].WesternBlotAnalysis[1]CellLine:HEK293AcellsConcentration:50μMIncubationTime:1,4,8hResult:Time-anddose-dependentlytriggeredformationofLC3punctaandincreasedthelevelsofLC3BII.WesternBlotAnalysis[1]CellLine:HEK293AcellsConcentration:25μMIncubationTime:1hResult:LedtocompleteinactivationofmTORC1signaling,asshownbyreducedlevelsofphosphorylatedcanonicalsubstrates,S6kinase1(S6K1),4EBP1,andULK1.Immunofluorescence[1]CellLine:HEK293AcellsConcentration:50μMIncubationTime:4hResult:LedtosignificantlyincreasedacidificationofthelysosomeinHEK293Acells,andthis2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEheightenedacidificationwasblockedbyBafA1.Immunofluorescence[1]CellLine:IPTG-inducibleGFP-TDP43U2OSosteosarcomacelllinemodelConcentration:25μMIncubationTime:7hResult:ReducedIPTG-inducedTDP43aggregatesby75%.体内研究EN6(50mg/kg;i.p.;single)inhibitsmTORC1andactivatesautophagyinvivo[1].AnimalModel:Six-week-oldmaleC57BL/6mice[1].Dosage:50mg/kgAdministration:Intraperitonealinjection;singleResult:SignificantlyinhibitedmTORC1signalinginbothskeletalmuscleandheart,asdemonstratedbyreducedphosphorylationofS6,4EBP1andULK1.StronglyactivatedautophagyasshownbyheightenedLC3BIIlevelsandreducedp62levels.户使⽤本产品发表的科研⽂献•ProcNatlAcadSciUSA.2022Oct25;119(43):e2207280119.•NeurochemRes.2022Oct15.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ChungCY,etal.CovalenttargetingofthevacuolarH+-ATPaseactivatesautophagyviamTORC1inhibition.NatChemBiol.2019Aug;15(8):776-785.McePdfHeightCaution:Producthasnotb