Clozapine-N-oxide-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEClozapineN-oxideCat.No.:HY-17366CASNo.:34233-69-7分?式:C??H??ClN?O分?量:342.82作?靶點(diǎn):mAChR;DopamineReceptor;DrugMetabolite作?通路:GPCR/GProtein;NeuronalSignaling;MetabolicEnzyme/Protease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(291.70mM)掃描?維碼，H2O:1mg/mL(2.92mM;Needultrasonic)運(yùn)?溶解?案計(jì)算器*"≥"meanssoluble,butsaturationunknown.獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9170mL14.5849mL29.1698mL5mM0.5834mL2.9170mL5.8340mL10mM0.2917mL1.4585mL2.9170mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶1.請(qǐng)依序添加每種溶劑：1%DMSO99%saline2.Solubility:≥0.1mg/mL(0.29mM);Clearsolution請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(7.29mM);Clearsolution此?案可獲得≥2.5mg/mL(7.29mM，飽和度未知)的澄溶液。1/3www.MedChemEwww.MedChemE以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述3.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.29mM);Clearsolution此?案可獲得≥2.5mg/mL(7.29mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶4.液中，混合均勻。請(qǐng)依序添加每種溶劑：5%DMSO40%PEG3005%Tween-8050%saline5.Solubility:≥0.5mg/mL(1.46mM);Clearsolution請(qǐng)依序添加每種溶劑：5%DMSO95%(20%SBE-β-CDinsaline)Solubility:≥0.5mg/mL(1.46mM);ClearsolutionBIOLOGICALACTIVITY?物活性ClozapineN-oxide?種Clozapine的主代謝產(chǎn)物，也?種?毒蕈堿設(shè)計(jì)受體(DREADDs)激動(dòng)劑。ClozapineN-oxide可激活DREADD受體hM3Dq和hM4Di。ClozapineN-oxide可以穿過(guò)?腦屏障。Clozapine?種有效的多巴胺拮抗劑，也?種有效的選擇性毒蕈堿M4受體(muscarinicM4receptor)(EC50為11nM)激動(dòng)劑。IC50&TargetHumanmuscarinicdesignerreceptors(DREADDs)[1]體外研究ClozapineN-oxide(CNO)canbindtonon-DREADDreceptorsatconcentrationsrequiredforDREADDactivation,andundergoesreverse-metabolismtoitsparentcompoundclozapine,anatypicalantipsychoticthatactsatavarietyofpharmacologicaltargetsandproducesnumerousphysiologicalandbehavioraleffects[2].體內(nèi)研究Afterasingleintraperitoneal(i.p.)injectionofClozapineN-oxide(1mg/kg)intomice,ClozapineN-oxide(CNO)plasmalevelspeakat15minandareverylowafter2h.Despitetheshortplasmahalf-lifeofCNOinmice,thebiologicaleffectsthathavebeendescribedafteracutetreatmentofDREADD-expressingexperimentalanimalsareusuallymuchlonger(6-10h)[1].戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2020Nov27;11(1):6045.?NatCommun.2020Jun5;11(1):2847.?BiolPsychiatry.2017May1;81(9):737-747.?ProcNatlAcadSciUSA.2019Aug13;116(33):16583-16592.?CellRep.2021Mar23;34(12):108889.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WessJ,etal.NoveldesignerreceptorstoprobeGPCRsignalingandphysiology.TrendsPharmacolSci.2013Jul;34(7):385-92.2/3www.MedChemEwww.MedChemE[2].SilvaRR,etal.EvaluationofFunctionalSelectivityofNSC170973,Clozapine,andLASSBio-579,anExperimentalCompoundWithAntipsychotic-LikeActionsinRodents,atGProteinandArrestinSignalingDownstreamoftheDopamineD2Receptor.FrontPharmacol.2019Jun4;10:628.[3].ZornSH,etal.ClozapineisapotentandselectivemuscarinicM4receptoragonist.EurJPharmacol.1994Nov15;269(3):R1-2.[4].ManvichDF,etal.TheDREADDagonistclozapineN-oxide(CNO)isreverse-metabolizedtoclozapineandproducesclozapine-likeinteroceptivestimuluseffectsinratsandmice.SciRep.2018Mar1;8(1):3840.[5].vanderPeetPL,etal.GramscalepreparationofclozapineN-oxide(CNO),asyntheticsmallmoleculeactuatorformuscarinicacetylcholineDREADDs.MethodsX.2018Mar23;5:257-267.[6].JosephCichon,etal.Branch-specificdendriticCa(2+)spikescausepersistentsynapticplasticity.Nature.2015Apr9;520(7546):180-5.McePdfHeight關(guān)注MCE中國(guó)公眾號(hào)，

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