ML402-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEML402Cat.No.:HY-104027CASNo.:298684-44-3分⼦式:C₁₄H₁₄ClNO₂S分⼦量:295.78作⽤靶点:PotassiumChannel作⽤通路:MembraneTransporter/IonChannel储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(338.09mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM3.3809mL16.9045mL33.8089mL5mM0.6762mL3.3809mL6.7618mL10mM0.3381mL1.6904mL3.3809mL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>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(8.45mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.45mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性ML402，⼀种噻吩甲酰胺，⼀种选择性的K2P2.1(TREK-1)和K2P10.1(TREK-2)活化剂，对K2P4.1(TRAAK)⽆明显作⽤。IC50&TargetTREK-1/2[1]体外研究Xenopusoocytetwo-electrodevoltage-clampmeasurementsshowthatML335andML402activateK2P2.1andK2P10.1butnotK2P4.1(14.3±2.7μM,K2P2.1-ML335;13.7±7.0μM,K2P2.1-ML402;5.2±0.5μM,K2P10.1-ML335;and5.9±1.6μM,K2P10.1-ML402).TheK2PmodulatorpockethasasingledifferenceamongTREKsubfamilymembersatthecation-πinteractionposition,K2P2.1Lys271,whichisalsoalysineinK2P10.1butaglutamineinK2P4.1.SwappingtheLys271equivalentbetweenK2P2.1andK2P4.1resultsinaclearphenotypereversalforML335andM402activation.K2P2.1(K271Q)isinsensitivetoML335andML402,whereasK2P4.1(Q258K)respondstobothwithasimilarEC50toK2P2.1(14.3±2.7μM,K2P2.1-ML335;16.2±3.0μM,K2P4.1(Q258K)-ML335;13.7±7.0μM,K2P2.1-ML402;13.6±1.5μM,K2P4.1(Q258K)-ML402)butwithalowermagnituderesponsethanK2P2.1[1].PROTOCOLKinaseAssay[1]K2P2.1crystML335andML402complexcrystalsgrowinthesameconditionsasK2P2.1cryst,buttheproteinisincubatedforatleast1hwith2.5mMofactivator(includingML402)beforesettingthecrystalplates.ML335andML402areinsolubleinaqueoussolutions,sotheyaredissolvedin100%DMSOataconcentrationof500mM.Theneachcompoundisdiluted1:100inSECbufferto5mMconcentration,givingamilkysolution.Thissolutionismixed1:1toK2P2.1crystpreviouslyconcentratingto12mg/mL.TheK2P2.1crystML402mixtureresultsinaclearsolution,whilethemixturewithML335isslightlymilky.Thesamplesarebrieflycentrifugedinatable-topcentrifuge(10,000×g)toremoveanyinsolublematerialbeforesettingthecrystalplates.Dose-responseexperimentsarecarriedbyfirstpreparingaDMSOstocksolutionofeachactivator(includingML402)ataconcentrationof100mM.Owingtothelowsolubilityofthecompoundsthehighesttestconcentrationsinrecordingsolutionare100μMand80μMforML335andML402,respectively.Otherconcentrationsarepreparedbyserialdilutionsofthe100μMsolutioninrecordingbuffersupplementingwith0.1%DMSO[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].LolicatoM,etal.K2P2.1(TREK-1)-activatorcomplexesrevealacrypticselectivityfilterbindingsite.Nature.2017Jul20;547(7663):364-368.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producth