NGP555-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENGP555Cat.No.:HY-108714CASNo.:1304630-27-0分?式:C??H??FN?S分?量:406.52作?靶點:γ-secretase作?通路:NeuronalSignaling;StemCell/Wnt儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(61.50mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4599mL12.2995mL24.5990mL5mM0.4920mL2.4599mL4.9198mL10mM0.2460mL1.2300mL2.4599mL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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(6.15mM);Suspendedsolution;Needultrasonic1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.15mM);ClearsolutionBIOLOGICALACTIVITY?物活性NGP555?個γ-分泌酶(γ-secretase)調(diào)節(jié)劑。IC50&Targetγ-secretase[1]體外研究NGP555potentlylowersAβ42incellcultures(9nM)whileincreasingshorterformsofAβ[1].體內(nèi)研究NGP555significantlylowersAβ42inthecerebrospinalfluid(CSF)attimepointsfrom8to10hourspostdose,panelBshowsthatreductionofAβcerebrospinalfluid(CSF)levelsissignificantat3.75mg/kgofNGP555andabove,andpanelCshowsanincreaseinAβ38levelsat15mg/kgofNGP555andabove.WhencombiningthereductionofAβ42withanincreaseinAβ38,NGP555iseffectiveatraisingCSFAβ38/42ratioat1.87mg/kgandabove(panelD).NGP555-treatedTgmiceshowasignificantprotectionfromdeclineinperformancewith>65%lessdecline(P[1].PROTOCOLCellAssay[1]SH-SY5Y-APPcells,Tg2576mixedbraincultures,orC57mixedbrainculturesaretreatedwithvariousconcentrationsofNGP555intriplicatewells,for18hours.MediaiscollectedandanalyzedforAβpeptidesusingtriplexELISA(Aβ38andAβ42)[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalForCSFstudies,NormalSprague-Dawleymalerats(250to300g)areadministeredNGP555in80%PEGAdministration[1]orallyorvehicleonly,n=10/group.Ratsaredosedonce-dailyforasingle-doseor14daysofdosing.Afterthefinaldose,cerebrospinalfluid(CSF)samplesareeithercollectedatvaryingtimepointsorasingletimepointpost-lastdose.Ratsaredeeplyanesthetizedwithisoflurane,andCSFiscollectedfromthecisternamagna.SamplesaretestedforAβlevel.ForY-mazestudy,transgenicmice(Tg2576lineexpressingtheAPP-Swemutation)andnon-transgenicage-matchedlittermates(n=aminimumof12/group)aretreatedwithvehicle,NGP555(25mg/kg)once-dailyfor30consecutivedays(startingat5monthsofage).At6months,miceareassessedontheY-mazebehaviortest[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].KounnasMZ,etal.NGP555,aγ-SecretaseModulator,LowerstheAmyloidBiomarker,Aβ42,inCerebrospinalFluidwhilePreventingAlzheimer'sDiseaseCognitiveDeclineinRodents.AlzheimersDement(NY).2017Jan;3(1):65-73.McePdfHeightCaution:Producthasnotbeenf