AS1842856-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAS1842856Cat.No.:HY-100596CASNo.:836620-48-5分⼦式:C₁₈H₂₂FN₃O₃分⼦量:347.38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(14.39mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.8787mL14.3935mL28.7869mL5mM0.5757mL2.8787mL5.7574mL10mM0.2879mL1.4393mL2.8787mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:1mg/mL(2.88mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1mg/mL(2.88mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.67mg/mL(4.81mM);Clearsolution4.请依序添加每种溶剂：6%HP-β-CDinsalineSolubility:10mg/mL(28.79mM);Suspensionsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性AS1842856⼀种特异性的Foxo1抑制剂，IC50为30nM，AS1842856有效抑制⾃噬(autophagy)[1]。AS1842856仅通过与FoxO1结合⽽降低FoxO1的活性，⽽不响其转录和蛋⽩质表达[2]。IC50&TargetIC50:30nM(Foxo1)[1]体外研究AS1842856potentlyinhibitshumanFoxo1transactivationandreducesglucoseproductionthroughtheinhibitionofglucose-6phosphataseandphosphoenolpyruvatecarboxykinasemRNAlevelsinarathepaticcellline[1].AfterAS1842856treatment,thereisnosignificantdifferenceintheproteinexpressionofp-FoxO1andFoxO1comparedwiththecontrolgroup,buttheexpressionofp-Aktisdecreasedcomparedwiththecontrolgroup[2].体内研究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.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师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