ML218-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEML218Cat.No.:HY-103309CASNo.:1346233-68-8分⼦式:C₁₉H₂₆Cl₂N₂O分⼦量:369.33作⽤靶点:CalciumChannel作⽤通路:MembraneTransporter/IonChannel;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(338.45mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7076mL13.5380mL27.0761mL5mM0.5415mL2.7076mL5.4152mL10mM0.2708mL1.3538mL2.7076mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥6.25mg/mL(16.92mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性ML218⼀种有效的，选择性的和⼝服活性的T型Ca2+通道(Cav3.1，Cav3.2，Cav3.3)抑制剂，对Cav3.2和Cav3.3的IC50分别为310nM和270nM。ML218抑制丘脑底核(STN)神经元的爆发活动。ML218对L或N型钙通道，KATP或hERG钾通道⽆明显抑制作⽤。ML218可以穿透⾎脑屏障。IC50&TargetIC50:310nM(Cav3.2),270nM(Cav3.3),and150nM(Ca2+flux)[1]体外研究Inplasmaproteinbindingstudies(equilibriumdialysis),ML218possessesgoodfreefractioninbothratandhuman.IntrinsicclearanceexperimentsinlivermicrosomesindicatedthatML218ishighlyclearedinrat(CLint=115mL/min/kg),butlowtomoderatelyclearedinhumanlivermicrosomes(CLint=12.7mL/min/kg)[1].体内研究ML218(0.03-30mg/kg;oraladministration;once;maleSprague-Dawleyrats)treatmentreversescatalepticbehaviorinratsinducedbya0.75mg/kgdoseofhaloperidol[1].FreebrainandplasmaconcentrationsofML218increasesinadoseproportionalmanneracrossthedoserange(3mg/kg:[plasma]=98nM,[brain]=1.66μM;10mg/kg:[plasma]=282nM,[brain]=5.03μM;30mg/kg:1.2μM,[brain]=17.7μM)[1].NoncompartmentalpharmacokineticanalysisindicatesML218(1mg/kg,IV)hasameanresidencetime(MRT)ofnearly7h,avaluewhichisconsistentwithitsterminalhalf-life(t1/2=7h)[1].AnimalModel:MaleSprague-Dawleyrats(275-299g)inducedbyhaloperidol[1]Dosage:0.03mg/kg,0.1mg/kg,0.3mg/kg,1mg/kg,3mg/kg,10mg/kg,30mg/kgAdministration:Oraladministration;onceResult:Reversedcatalepticbehaviorinratsinducedbya0.75mg/kgdoseofhaloperidol.REFERENCES[1].XiangZ,etal.TheDiscoveryandCharacterizationofML218:ANovel,CentrallyActiveT-TypeCalciumChannelInhibitorwithRobustEffectsinSTNNeuronsandinaRodentModelofParkinson'sDisease.ACSChemNeurosci.2011Dec21;2(12):730-742.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapp