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

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEZuranoloneCat.No.:HY-103040CASNo.:1632051-40-1分?式:C??H??N?O?分?量:409.56作?靶點(diǎn):GABAReceptor作?通路:MembraneTransporter/IonChannel;NeuronalSignaling儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(244.16mM;Needultrasonic)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.4416mL12.2082mL24.4164mL5mM0.4883mL2.4416mL4.8833mL10mM0.2442mL1.2208mL2.4416mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:2.5mg/mL(6.10mM);Suspendedsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.10mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.10mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:2.5mg/mL(6.10mM);Suspendedsolution;Needultrasonic5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.10mM);ClearsolutionBIOLOGICALACTIVITY?物活性Zuranolone?個(gè)?服有效的GABAA受體的神經(jīng)活性類醇正向變構(gòu)調(diào)節(jié)劑,對(duì)α1β2γ2和α4β3δGABAA受體的EC50值分別為296和163nM。IC50&TargetEC50:296nM(α1β2γ2GABAAreceptor),163nM(α4β3δGABAAreceptor)[1]體外研究ZuranoloneisapotentGABAAreceptoragonistwithEC50sof296and163nMforα1β2γ2andα4β3δGABAAreceptors,respectively.Zuranoloneiscurrentlybeingstudiedinparallelphase2clinicaltrialsforthetreatmentofpostpartumdepression(PPD)andmajordepressivedisorder(MDD).Zuranoloneshows>30μMinhibitioninacardiacpanelofeightrelevantcardiacionchannels.At10μMconcentrationofZuranolone,onlybindingattheglycine(57%),sigmareceptors(88%),andinhibitionofthetransientreceptorpotentialvanilloid1(TRPV1,95%)isnoted[1].體內(nèi)研究AcuteadministrationofZuranolone(0.3to10mg/kg,ip)effectivelyreducespentylenetretazol(PTZ)-inducedseizuresinmice(MECplasma=85nM)aswellasproducesadose-dependentanticonvulsanteffectinthemouse6Hzelectricalstimulationmodel.Intheratmodelofstatusepilepticus(SE),Zuranolone(0.3to5mg,iv)abolishesbothbehavioralandelectrographicseizureactivity,evenwhenadministered60minafterinductionofSE.AdditionalPKstudiesofZuranoloneindogshowlowclearance([1].PROTOCOLAnimalInvivopharmacokineticparametersaredeterminedinmaleSpragueDawleyrats(of200to300ginweight),Administration[1]maleCD-1mice(15to25ginweight),andmalebeagledogs(8to12kginweight).DosesofZuranoloneforintravenous(IV)andoraladministration(PO)areformulatedassolutionsinSBECD.ZuranoloneisdosedIV(5mg/kg,2.5mL/kg)orbyoralgavage(20mg/kg,10mL/kg).AnimalsintheIVgrouparesampledat0.083,0.25,1,2,4,and8hourspost-doseandPOanimalsaresampledat0.5,1,2,4,and8hourspostdose.BrainsamplesfromtheIVgrouparealsocollectedat1hourpost-dose.BloodsamplesarecollectedintotubestreatedwithK2-EDTA,thencentrifugedat2000gat4°Cfor15min.Plasmaisisolatedandfrozenat-70°Cuntilextraction[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JBiolChem.2020Aug14;295(33):11495-11512.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MartinezBotellaG,etal.NeuroactiveSteroids.2.3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one:AClinicalNextGenerationNeuroactiveSteroidPositiveAllostericModulatorofthe(γ-AminobutyricAcid)AReceptor.JMedCheMcePd