Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEML218Cat.No.:HY-103309CASNo.:1346233-68-8分?式:C??H??Cl?N?O分?量:369.33作?靶點(diǎn):CalciumChannel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:125mg/mL(338.45mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.7076mL13.5380mL27.0761mL5mM0.5415mL2.7076mL5.4152mL10mM0.2708mL1.3538mL2.7076mL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(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：10%DMSO>>90%cornoilSolubility:≥6.25mg/mL(16.92mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性ML218?種有效的，選擇性的和?服活性的T型Ca2+通道(Cav3.1，Cav3.2，Cav3.3)抑制劑，對(duì)Cav3.2和Cav3.3的IC50分別為310nM和270nM。ML218抑制丘腦底核(STN)神經(jīng)元的爆發(fā)活動(dòng)。ML218對(duì)L或N型鈣通道，KATP或hERG鉀通道?明顯抑制作?。ML218可以穿透?腦屏障。IC50&TargetIC50:310nM(Cav3.2),270nM(Cav3.3),and150nM(Ca2+flux)[1]體外研究Inplasmaproteinbindingstudies(equilibriumdialysis),ML218possessesgoodfreefractioninbothratandhuman.IntrinsicclearanceexperimentsinlivermicrosomesindicatedthatML218ishighlyclearedinrat(CLint=115mL/min/kg),butlowtomoderatelyclearedinhumanlivermicrosomes(CLint=12.7mL/min/kg)[1].體內(nèi)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