Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETacrinehydrochloride(hydrate)Cat.No.:HY-B2244CASNo.:206658-92-6分?式:C??H??N?.xHCl.xH?O作?靶點(diǎn):Cholinesterase(ChE)作?通路:NeuronalSignaling儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗H2O:100mg/mL(Needultrasonic)DMSO:32mg/mL(Needultrasonicandwarming)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(sealedstorage,awayfrommoisture)。-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(InfinitymM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(InfinitymM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(InfinitymM);ClearsolutionBIOLOGICALACTIVITY?物活性Tacrinehydrochloride(hydrate)?酰膽堿酯酶(AChE)和丁酰膽堿酯酶(BChE)的抑制劑，其IC50值分別為31nM和25.6nM。1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIC50&TargetIC50:31nM(AChE),25.6nM(BChE)體外研究Tacrinehydrochloride(hydrate)(12.5to37.5nM)inhibitsvenomacetylcholinesteraseaswellashumanserumbutyrylcholinesteraseinaconcentration-dependentmanner.TheIC50is31nMforsnakevenomAChEand25.6nMforhumanBChE[1].體內(nèi)研究PretreatmentwithTacrinehydrochloride(hydrate)alsomodifiesabsolutelevelsofcocaineself-administrationduringreacquisition.Bodyweightdeclinesapproximatelyone-halfpercentoverfourdaysoftreatmentwithintravenousTacrinehydrochloride(hydrate).DeliveryofTacrinehydrochloride(hydrate)byosmoticpumpdoesnotaltereitherlinear-orrepeated-cocaine-inducedlocomotoractivity.ThereisnosignificantmaineffectorinteractionwithTacrinehydrochloride(hydrate)treatmentonactiveleverrespondingduringreinstatement.Posthoccomparisonsindicatethatratsself-administeringcocainehassignificantlyloweralkalinephosphataselevels,relativetoTTacrinehydrochloride(hydrate)-butnotsaline-treatedratsevaluatedbyconditioned-placepreference[2].PROTOCOLKinaseAssay[1]ThekineticparametersoftheinteractionbetweenTacrinehydrochloridehydrateandcholinesterasearedeterminedusingthedoublereciprocalplotanalyzedoverarangeofacetylthiocholineconcentrations(0.05to1mM)intheabsenceandinthepresenceofTacrinehydrochloridehydrate(12.5to37.5nM).IC50isdeterminedbypercentageresidualactivityversusconcentrationofTacrinehydrochloridehydrate[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMaleWistarratsat9weeksofageareusedinthisstudy.Assoonasratsexhibitastablepatternofself-Administration[2]administrationunderfixed-ratio-5(FR-5)witha20-secondtimeout,sessionsarediscontinuedover24hoursandratsareleftundisturbedinhomecages,attachedtoafluidswivelandsteel-coiltether.Thisinitialwashoutintervalisassessedasmorethanadequatetoallowclearanceofplasmacocaine,whichhasahalf-lifeoflessthan20minutesinrats.Beginningonthefollowingday,10mg/kg-dayofTacrinehydrochloridehydrateorvehicle(saline)isadministeredasachronicinfusionover4days,deliveredintravenouslyat4.0mlperday.Aftercompletionoftheseinfusions,ratsarethenleftundisturbedinhomecagesforanadditionaltwodays.ThissecondwashoutperiodpermitscompleteclearanceofTacrinehydrochloridehydrate,whichhasahalf-lifeoflessthantwohoursinratbrain.Cocaineself-administrationisthenre-initiatedunderFR-5witha20-secondtime-outperiod.TodeterminepersistenteffectsofTacrinehydrochloridehydrate,thepatternofself-administrationismonitoredoversixadditionalsessions[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellDeathDis.2022Jan10;13(1):48.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].AhmedM,etal.Inhibitionoftwodifferentcholinesterasesbytacrine.ChemBiolInteract.2006Aug25;162(2):165-71.[2].GrasingK,etal.Enduringeffectsoftacrineoncocaine-reinforcedbehavior:Analysisbyconditioned-placepreference,temporalseparationfromdrugreward,andreinstatement.Pharmaco