NS8593-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemENS8593Cat.No.:HY-137952CASNo.:875755-39-8分⼦式:C₁₇H₁₇N₃分⼦量:263.34作⽤靶点:PotassiumChannel;TRPChannel作⽤通路:MembraneTransporter/IonChannel;NeuronalSignaling储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性NS8593⼀种SKchannel(⼩电导钙激活钾通道)抑制剂。NS8593可逆性地抑制重组SK3介导的电流(⼈SK3和⼤⿏SK3)。NS8593以Ca2+依赖的⽅式抑制所有SK1-3亚型(在0.5μMCa2+浓度下，Kd分别为0.42、0.60和0.73μM)。NS8593对中等电导和⼤电导的Ca2+激活的K+通道(分别为hlk和hBK通道)没有响。NS8593还可以抑制TRPM7(⿊素抑制素相关TRP阳离⼦通道7)(IC50=1.6mM)。NS8593可⽤于中枢神经系统(CNS)相关疾病的研究[1][2]。体外研究NS8593reversiblysuppressesSK3current;IC50is91nMinHEK293cells[1].NS8593(10μM,4min)hasnosignificanteffectonhumanIK(hIK)currentinHEK293cells[1].NS8593's(3μM)inhibitoryeffectonHEK293cellsdecreasedwithincreasingintracellularCa2+concentration(Kd=0.47μMat0.3μMCa2+andKd=14μMat10μMCa2+)[1].NS8593(3μM,4min)shiftstheCa2+activationcurvetotheright(EC50increasesfrom0.43μMto1.6μM)andreducestheHillcoefficient(from5.6to2.0)inHEK293cells[1].NS8593cannotdisplacethebindingoflapaminataconcentrationof10μM,whilelapamin,UCL1684anddequaliniumcompletelyinhibitthebindinginHEK293cells[1].NS8593(1μM,30μM)reversiblysuppressesTRPM7currentinHEK293cells;1μMNS8593partiallysuppressesit,and30μMalmostcompletelysuppressesit;insolutionwithoutMg2+,theIC50is1.6μM;inthepresenceof300μMMg2+,theIC50increasesto5.9μM[2].NS8593(10-100μM)inhibitsTRPM3currentinHEK293cells(IC50=26.7μM),butisspecificforTRPM7at10μManddoesnotaffectTRPM8,TRPM2,TRPM5,TRPC6,TRPV1orTRPA1[2].NS8593(10-30μM,24-48h),followinglong-termexposure,inhibitsTRPM7-dependentchangesinHEK293cellmotilityandmorphology,confirmingtheroleofTRPM7incellmigration[2].CellMigrationAssay[2]1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:Tetracycline-inducibleHEK293cellsexpressinghumanTRPM7Concentration:10μM,30μMIncubationTime:24hResult:Significantlyreducedtheareaofwoundclosure.REFERENCES[1].1.StrøbaekD,etal.InhibitorygatingmodulationofsmallconductanceCa-activatedK+channelsbythesyntheticcompound(R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine(NS8593)reducesafterhyperpolarizingcurrentinhippocampalCA1neurons.MolPharmacol.2006Nov;70(5):1771-82.[2].2.ChubanovV,etal.NaturalandsyntheticmodulatorsofSK(K(ca)2)potassiumchannelsinhibitmagnesium-dependentactivityofthekinase-coupledcationchannelTRPM7.BrJPharmacol.2012Jun;166(4):1357-76.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapp