Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEML402Cat.No.:HY-104027CASNo.:298684-44-3分?式:C??H??ClNO?S分?量:295.78作?靶點:PotassiumChannel作?通路:MembraneTransporter/IonChannel儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥100mg/mL(338.09mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.3809mL16.9045mL33.8089mL5mM0.6762mL3.3809mL6.7618mL10mM0.3381mL1.6904mL3.3809mL請根據(jù)產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(8.45mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.45mM);ClearsolutionBIOLOGICALACTIVITY?物活性ML402，?種噻吩甲酰胺，?種選擇性的K2P2.1(TREK-1)和K2P10.1(TREK-2)活化劑，對K2P4.1(TRAAK)?明顯作?。IC50&TargetTREK-1/2[1]體外研究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?邊的抑制劑?師www.MedChemECaution:Producth