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

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.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)H2O:1mg/mL(2.92mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.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；?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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(7.29mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.29mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.29mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥0.5mg/mL(1.46mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥0.5mg/mL(1.46mM);Clearsolution6.請(qǐng)依序添加每種溶劑：PBSSolubility:2.44mg/mL(7.12mM);Clearsolution;Needultrasonicandwarmingandheatto60°CBIOLOGICALACTIVITY?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?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)?CellMetab.2022Feb1;34(2):285-298.e7.?NatCommun.2022Apr25;13(1):2233.?NatCommun.2020Nov27;11(1):6045.?NatCommun.2020Jun5;11(1):2847.?BiolPsychiatry.2017May1;81(9):737-747.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].WessJ,etal.NoveldesignerreceptorstoprobeGPCRsignalingandphysiology.TrendsPharmacolSci.2013Jul;34(7):385-92.[2].SilvaRR,etal.EvaluationofFunctionalSelectivityofNSC170973,Clozapine,andLASSBio-579,anExperimentalCompoundWithAntipsychotic-LikeActionsinRodents,atGProteinandArrestinSignalingDownstreamoftheDopamineD2Receptor.FrontPharmac[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.McePdfHei