Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELanabecestatCat.No.:HY-100740CASNo.:1383982-64-6Synonyms:AZD3293;LY3314814分?式:C??H??N?O分?量:412.53作?靶點:Beta-secretase作?通路:NeuronalSignaling儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:≥100mg/mL(242.41mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4241mL12.1203mL24.2407mL5mM0.4848mL2.4241mL4.8481mL10mM0.2424mL1.2120mL2.4241mL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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：1%DMSO>>99%salineSolubility:0.5mg/mL(1.21mM);Suspendedsolution;Needultrasonic2.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.06mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.06mM);Clearsolution4.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.06mM);Clearsolution5.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(6.06mM);Clearsolution6.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.06mM);ClearsolutionBIOLOGICALACTIVITY?物活性Lanabecestat(AZD3293)?種具有?服活性的，可透過?腦屏障的BACE1抑制劑，Ki值為0.4nM。Lanabecestat可?于阿爾茲海默癥的研究[1]。IC50&TargetKi:0.4nM(BACE1)[1]體外研究LanabecestatactsasafullinhibitorofBACE1invitro,withacompetitiveandreversiblemechanismofactiontowardsthehBACE1activesite.Lanabecestatdisplaysaveryhightargetaffinityandamarkedlyslowtargetoff-rate.Theoff-rateoflanabecestathasanestimatedt1/2ofapproximately9h.LanabecestatdisplayspMpotencyinprimaryneuronculturesfrommiceandguineapigsandinSH-SY5Ycellsover-expressingAβPP(IC50=610pM,310pM,and80pM,respectively).Theinvitroplasmaproteinbindingoflanabecestatisdeterminedbyequilibriumdialysisusingmouse,rat,guineapig,dog,andhumanplasma.Thecompoundisstableintheplasmaofthesespeciesforatleastthedurationoftheinvitroincubationperiod.Theunboundfractionsare1.3%to1.8%formice,4.2%to5.9%forrats,8.3%to10.3%forguineapigs,9.4%to10.3%fordogs,and7.7%to9.4%forhumanplasma.Themeanblood:plasmaratioof0.7inhumanbloodindicatesnosignificantassociationwithredbloodcells.Thefreefractioninthebraintissuebindingassayis4.5%[1].體內研究Inmice,guineapigs,anddogs,lanabecestatdisplayssignificantdose-andtime-dependentreductionsinplasma,cerebrospinalfluid,andbrainconcentrationsofAβ40,Aβ42,andsAβPPβ[1].PROTOCOLCellAssay[1]Cellsareincubatedwithdifferentlanabecestatconcentrationsfor5to16h,andthereleaseofsAβPPβ,Aβ1-40,Aβ1-42,orsAβPPαintothemediumisanalyzedusingkits.Cytotoxiceffectoflanabecestatisevaluatedinthecellplatesusingcellproliferation/cytotoxicitykit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalFemale7-to14-week-oldC57BL/6mice(n=6pertreatmentgroupandtimepoint)receivevehicleor2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration[1]lanabecestatsolutionat50,100,or200μmol/kg(20,41,or82mg/kg)asasingledoseviaoralgavage.Miceandguineapigsareanesthetized1.5,2,3,4,6,8,16,24,or48hafterthe(last)administrationofvehicleordrug.Cerebrospinalfluid(CSF)isaspiratedfromthecisternamagna,andplasmaisisolatedfrombloodcollectedbycardiacpunctureintoEDTAtubes.Theanimalsarethensacrificedbydecapitation,andthebrainsaredissectedintohemispheres[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].Eketj?llS,etal.AZD3293:ANovel,OrallyActiveBACE1InhibitorwithHighPotencyandPermeabilityandMarkedlySlowOff-RateKinetics.JAlzheimersDis.2016;50(4):1109