ML417-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEML417Cat.No.:HY-136390CASNo.:1386162-69-1分⼦式:C₂₂H₂₅N₃O₃分⼦量:379.45作⽤靶点:DopamineReceptor作⽤通路:GPCR/GProtein;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(131.77mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6354mL13.1770mL26.3539mL5mM0.5271mL2.6354mL5.2708mL10mM0.2635mL1.3177mL2.6354mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存⽅式和期限。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的⼯作液，建议您现⽤现配，当天使⽤；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分⽐指该溶剂在您配制终溶液中的体积占⽐)：1.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5mg/mL(13.18mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性ML417⼀种选择性的，可透过⾎脑屏障的D3多巴胺受体(D3R)激动剂，EC50为38nM。ML417促进D3R1/2MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemE介导的β-arrestin易位、G蛋⽩介导的信号传导和pERK磷酸化，对其他GPCR介导的信号传导响最⼩。ML417对毒素诱导的多巴胺能神经元变性具有神经保护作⽤。IC50&TargetD3Receptor38nM(EC50)体外研究ML417exhibitsaKifortheD3Rof1.24µM.ML417isafullandpotentagonistformultiplesignalingpathwaysassociatedwithD3Ractivation[1].ML417potentlyinhibitscAMPaccumulationwithanEC50of86nMandanefficacyidenticaltothatofdopamine.ML417exhibitssubmicromolaraffinityforonlythreeofthetargets,theβ1-adrenergic,5-HT2Bserotoninergic,andσ-1receptors.ML417stimulatesβ-arrestinrecruitmenttotheD3R-WTwithanEC50of1.4nM[1].ML417protects(0.005-5μM;24hours)D3R-expressingdopaminergicneuronsfrom6-OHDAinducedcelldeath[1].体内研究Invivopharmacokineticsexperimentsinmice(using20mg/kg;i.p.)revealsthatML417isbrainpenetrantandexhibitsaplasmahalf-lifeof3.44hoursandabrainhalf-lifeof4.23hours.ML417displaysaplasmaTmaxof0.5hoursandCmaxof6500ng/ml,andabrainTmaxof0.25hoursandCmaxof28000ng/ml[1].AnimalModel:6-8weekoldmaleC57BL/6mice[1]Dosage:20mg/kgAdministration:I.p.(PharmacokineticAnalysis)Result:Brainpenetrantandexhibitsaplasmahalf-lifeof3.44hoursandabrainhalf-lifeof4.23hours.DisplayedaplasmaTmaxof0.5hoursandCmaxof6500ng/ml,andabrainTmaxof0.25hoursandCmaxof28000ng/ml.REFERENCES[1].MoritzAE,etal.Discovery,Optimization,andCharacterizationofML417:ANovelandHighlySelectiveD3DopamineReceptorAgonist.JMedChem.2020;63(10):5526‐5567.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Fo