Lanabecestat-AZD3293-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELanabecestatCat.No.:HY-100740CASNo.:1383982-64-6Synonyms:AZD3293;LY3314814分⼦式:C₂₆H₂₈N₄O分⼦量:412.53作⽤靶点:Beta-secretase作⽤通路:NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(242.41mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4241mL12.1203mL24.2407mL5mM0.4848mL2.4241mL4.8481mL10mM0.2424mL1.2120mL2.4241mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：1%DMSO>>99%salineSolubility:0.5mg/mL(1.21mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.06mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.06mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.06mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(6.06mM);Clearsolution6.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.06mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Lanabecestat(AZD3293)⼀种具有⼝服活性的，可透过⾎脑屏障的BACE1抑制剂，Ki值为0.4nM。Lanabecestat可⽤于阿尔兹海默症的研究[1]。IC50&TargetKi:0.4nM(BACE1)[1]体外研究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].体内研究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—您⾝边的抑制剂⼤师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].EketjällS,etal.AZD3293:ANovel,OrallyActiveBACE1InhibitorwithHighPotencyandPermeabilityandMarkedlySlowOff-RateKinetics.JAlzheimersDis.2016;50(4):1109