EN6-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEN6Cat.No.:HY-128892CASNo.:1808714-73-9分?式:C??H??F?N?O?分?量:368.34作?靶點:Autophagy作?通路:Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:5mg/mL(13.57mM;Needultrasonic)Ethanol:1.11mg/mL(3.01mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.7149mL13.5744mL27.1488mL5mM0.5430mL2.7149mL5.4298mL10mM0.2715mL1.3574mL2.7149mL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：50%PEG300>>50%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:10mg/mL(27.15mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性EN6?種?分?體內(nèi)?噬(autophagy)激活劑，其共價靶向溶酶體v-ATP酶的ATP6V1A亞中的半胱氨酸277。EN6介導(dǎo)的ATP6V1A修飾使v-ATP酶與Rag解偶聯(lián)，導(dǎo)致mTORC1信號的抑制，增加溶酶體酸化，并激活?噬。EN6還能以溶酶體依賴的?式除TDP-43聚集物(額顳葉癡呆的致病因?)。體外研究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?邊的抑制劑?師www.MedChemEheightenedacidificationwasblockedbyBafA1.Immunofluorescence[1]CellLine:IPTG-inducibleGFP-TDP43U2OSosteosarcomacelllinemodelConcentration:25μMIncubationTime:7hResult:ReducedIPTG-inducedTDP43aggregatesby75%.體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ProcNatlAcadSciUSA.2022Oct25;119(43):e2207280119.?NeurochemRes.2022Oct15.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].ChungCY,etal.CovalenttargetingofthevacuolarH+-ATPaseactivatesautophagyviamTORC1inhibition.NatChemBiol.2019Aug;15(8):776-785.McePdfHeightCaution:Producthasnotb