Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAS1842856Cat.No.:HY-100596CASNo.:836620-48-5分?式:C??H??FN?O?分?量:347.38作?靶點:Autophagy作?通路:Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:5mg/mL(14.39mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.8787mL14.3935mL28.7869mL5mM0.5757mL2.8787mL5.7574mL10mM0.2879mL1.4393mL2.8787mL請根據產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，避免反復凍融造成的產品失效。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?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?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：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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沉淀、析出現象，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:1mg/mL(2.88mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.88mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(4.81mM);Clearsolution4.請依序添加每種溶劑：6%HP-β-CDinsalineSolubility:10mg/mL(28.79mM);Suspensionsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性AS1842856?種特異性的Foxo1抑制劑，IC50為30nM，AS1842856有效抑制?噬(autophagy)[1]。AS1842856僅通過與FoxO1結合?降低FoxO1的活性，?不響其轉錄和蛋?質表達[2]。IC50&TargetIC50:30nM(Foxo1)[1]體外研究AS1842856potentlyinhibitshumanFoxo1transactivationandreducesglucoseproductionthroughtheinhibitionofglucose-6phosphataseandphosphoenolpyruvatecarboxykinasemRNAlevelsinarathepaticcellline[1].AfterAS1842856treatment,thereisnosignificantdifferenceintheproteinexpressionofp-FoxO1andFoxO1comparedwiththecontrolgroup,buttheexpressionofp-Aktisdecreasedcomparedwiththecontrolgroup[2].體內研究OraladministrationofAS1842856todiabeticdb/dbmiceleadstoadrasticdecreaseinfastingplasmaglucoselevelviatheinhibitionofhepaticgluconeogenicgenes,whereasadministrationtonormalmicehasnoeffectonthefastingplasmaglucoselevel.TreatmentwithAS1842856alsosuppressesanincreaseinplasmaglucoselevelcausedbypyruvateinjectioninbothnormalanddb/dbmice[1].PROTOCOLCellAssay[1]RathepatomaFaocellsareculturedinDMEMwith5.5mMglucoseand10%FBS.GlucoseproductionrateismeasuredusingglucoseCII-testreagent.Inbrief,after18hoftreatmentwithAS1842856attheindicatedconcentrations,thecellsareishedthreetimeswithPBS.Thecellsarethenincubatedfor3hat37°Cin5%CO2inaglucoseproductionbuffer(glucose-freeDMEM,pH7.4,containing20mMsodiumpyruvate,withoutphenolred)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalAS1842856isdissolvedin6%cyclodextrinfororaladministration.PyruvateorglucosetolerancetestsareAdministration[1]performedinmalemiceaged7to9weeks.MiceareorallyadministeredeitherAS1842856dissolvedin6%cyclodextrinorvehicle(6%cyclodextrinonly)atthreetimepoints(8AM,6PM,and8AMonthesecondday).Foodisremovedafterinitialdosingandwithheldthroughoutthestudy(26-hfasting)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?ProcNatlAcadSciUSA.2021Nov16;118(46):e2105950118.?ExpMolMed.2021Sep;53(9):1307-1318.?Theranostics.2021Jul25;11(18):8624-8639.?Theranostics.2021Jul25;11(18):8624-8639.?RedoxBiol.2022Jun;52:102311.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].NagashimaT,etal.DiscoveryofnovelforkheadboxO1inhibitorsfortreatingtype2diabetes:improvementoffastingglycemiaindiabeticdb/dbmice.MolPharmacol.2010Nov;78(5):961-70.[2].HeJ,etal.TheresistanteffectofSIRT1inoxidativestress-inducedsenescenceofratnucleuspulposuscellisregulatedbyAkt-FoxO1pathway.BiosciRep.2019May10;39(5).pii:BSR20190112.Mce