Kv7-2-Kv7-3-activator-3-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemEKv7.2/Kv7.3activator-3Cat.No.:HY-175340CASNo.:1361107-81-4分子式:C₂₂H₂₀F₄N₂O₃分子量:436.4作用靶点:PotassiumChannel;TSPO作用通路:MembraneTransporter/IonChannel;NeuronalSignaling储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性Kv7.2/Kv7.3activator-3(GRT-X)是一种具有口服活性的Kv7.2/Kv7.3和TSPO激活剂。Kv7.2/Kv7.3activator-3激活Kv7.2/Kv7.3，Kv7.4，Kv7.5，EC50分别是0.37，2.06，0.75μM，结合TSPO，Ki分别为0.07μM(大鼠膜)，4.60μM(人U-118MG细胞)。Kv7.2/Kv7.3activator-3可防止小鼠和人类肌萎缩侧索硬化症/额颞叶痴呆星形胶质细胞条件培养基暴露后运动神经元的变性。Kv7.2/Kv7.3activator-3通过TSPO和Kv7.2/3激活刺激背根神经节轴突生长。Kv7.2/Kv7.3activator-3在癫痫发作模型中具有抗癫痫功效。Kv7.2/Kv7.3activator-3减轻糖尿病神经病变患者的痛觉过敏，促进大鼠颈神经病变后神经元的存活和再生，加速感觉神经元和运动神经元的正常功能恢复。IC50&TargetKV7.2KV7.4KV7.50.37μM(EC50)2.06μM(EC50)0.75μM(EC50)体外研究Kv7.2/Kv7.3activator-3(6.25-25μM,20days)showsreductioninmotoneurons(MNs)deathinSCOCs[1].Kv7.2/Kv7.3activator-3(0.1-10μM,4days)doesnotreduceMNssurvivalupto2.5μMinratprimaryspinalcordcultures(VSCNs)[1].Kv7.2/Kv7.3activator-3(6.25-25μM,4days)preservesMNsviabilityinSCOCstreatedwithhumanSOD1G93A-ACM/SOD1D90A-ACM/TDP43A90V-ACM[1].Kv7.2/Kv7.3activator-3(1-2.5μM,4days)rescuesMNsdeath,reducesDCFcountsinVSCNstreatedwithhumanSOD1G93A-ACM/SOD1D90A-ACM/TDP43A90V-ACM[1].Kv7.2/Kv7.3activator-3(10μM,4days)enhancesthelengthanddensityoftheneuritenetwork,withamarkedincreaseinAUCinembryonicC57BL6/JDRG[2].Kv7.2/Kv7.3activator-3(10μM,8days)maintainspositiveeffectonaxonalgrowth,increasesAUCsinE13.5DRGexplants[2].Kv7.2/Kv7.3activator-3(10μM,4days)inducesincreasedexpressionofgenesinvolvedinmyelination,1/5 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemESchwanncellandneuronaldevelopmentanddifferentiation,andaxonalstructureinE13.5DRGexplants[2].Kv7.2/Kv7.3activator-3(10μM,4days)hasnoeffectonneuriteoutgrowth,butincreasesexpressionofgenesassociatedwithmyelinationandSchwanncellandneuronaldevelopment,butnotgenesinvolvedinaxonalstructureinDIV4embryonicTSPO-KODRGexplants[2].Kv7.2/Kv7.3activator-3activatesneuronalhKv7.2/3,hKv7.4,andhKv7.5channelswithahigherpotencythanretigabineinCHO-K1cells[3].Kv7.2/Kv7.3activator-3(10μM)leadsapotentandefficienthyperpolarizationoftherestingmembranepotential(EC50=0.201μM,maximalhyperpolarization:13.2mV)inculturedratDRGneurons[4].Kv7.2/Kv7.3activator-3(10μM)bindstoratheartmembraneswithhighandtohumanU-118MGglioblastomacellswithmoderateaffinityinTSPObindingassays,enhancespregnenolonesynthesisbyculturedratC6gliomacellsinTSPOfunctionalassay[4].Immunofluorescence[1]CellLine:SCOCstreatedwithSOD1G93A-ACM/SOD1D90A-ACMConcentration:6.25μM,12.5μM,25μMIncubationTime:4daysResult:PreservedMNviability.RT-PCR[1]CellLine:E13.5DRGexplantsConcentration:10μMIncubationTime:4daysResult:InducedasignificantincreaseinthemRNAexpressionofTSPO,Kv7.2,Kv7.3,myelin-relatedgenes(Mpz,MbpandPlp),Dhh,Krox20andCNPase,andincreasedthetotalmRNAexpressionlevelsofTfap2α,Stmn2,Peripherin,Cad19,andNfhgenes.RT-PCR[1]CellLine:SPO-KODRGexplantsConcentration:10μMIncubationTime:4daysResult:IncreasedKv7.2,Kv7.3,Mpz,Mbp,Plp,Dhh,CNPaseTfap2α,andCad19mRNAlevels,anddecreasedStmn2expression.体内研究Kv7.2/Kv7.3activator-3(10mg/kg,p.o.,once)increasesbrainlevelsofneurosteroidsandsteroidinSDratmodel[3].Kv7.2/Kv7.3activator-3(0-10mg/kg,p.o.,once)preventstheoccurrenceoftonicepilepticseizuresin2/5 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEMaximalelectroshockseizure(MES)seizuremaleWistarratsmodel[3].Kv7.2/Kv7.3activator-3(0-3mg/kg,p.o.,once)increasesseizurethresholdinElectroconvulsiveseizure(ECS)seizuremaleWistarratsmodel[3].Kv7.2/Kv7.3activator-3(0-100mg/kg,p.o.,once)increaseslatencytoclonicseizures,decreasestheincidenceoftonicseizuresinpentylenetetrazol(PTZ)seizuremaleWistarratsmodel[3].Kv7.2/Kv7.3activator-3(0-100mg/kg,p.o.,once)reducesincidenceoftonicconvulsionsinPTZseizuremaleSDratsmodel[3].Kv7.2/Kv7.3activator-3(0-10mg/kg,p.o.,once)reducestheincidenceofwild-runningandclonicseizures,andpreventstonicseizuresandmortalityinmaleRj:DBA/2micemodel[3].Kv7.2/Kv7.3activator-3(0-100mg/kg,p.o.,once)prevents6-HzseizuresinmaleNMRImicemodel[3].Kv7.2/Kv7.3activator-3(0.316-10mg/kg,p.o.,once)reduceshyperalgesiainStreptozotocin(STZ)(HY-13753)-inducedchronicneuropathicpain(CNP)SDratsmodel[4].Kv7.2/Kv7.3activator-3(5-10mg/kg,p.o.,once)promotesthesurvivalandregenerationofneurons,acceleratingtherecoveryofnormalfunctionsofsensoryneuronsandmotorneuronsinseverecervicalspinalnervecompressioninjurySDratsmodel[4].AnimalModel:MaleSDrat(200-230g)model[3]Dosage:10mg/kgAdministration:p.o.,onceResult:Increasedbrainlevelsofneurosteroids,including3α,5α-THPand3α,5α-THDOC,increased627%(pregnenolone),107%(progesterone),116%(5-α-dihydroprogesterone),132%(3α,5α-THP),4911%(deoxycorticosterone),1333%(5α-deoxycorticosterone),and1040%(3α,5α-THDOC),respectivelyinbrainsteroidlevels.AnimalModel:MESseizuremaleWistarrats(200-230g)model[3]Dosage:0mg/kg,1mg/kg,3mg/kg,10mg/kgAdministration:p.o.,onceResult:Preventedtheoccurrenceoftonicepilepticseizures,withanED50of3.7mg/kg.AnimalModel:ECSseizuremaleWistarrats(200-230g)model[3]Dosage:0mg/kg,0.3mg/kg,1mg/kg,3mg/kgAdministration:p.o.,onceResult:Increasedseizurethreshold.AnimalModel:PTZseizuremaleWistarrats(200-230g)model[3]Dosage:0mg/kg,10mg/kg,30mg/kg,100mg/kg3/5 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAdministration:p.o.,onceResult:Increasedlatencytoclonicseizures,decreasedtheincidenceofPTZ-inducedtonicseizureswithED50of37mg/kg.AnimalModel:PTZseizuremaleSDrats(200-230g)model[3]Dosage:0mg/kg,3mg/kg,10mg/kg,30mg/kg,100mg/kgAdministration:p.o.,onceResult:Reducedincidenceoftonicconvulsions.AnimalModel:MaleRj:DBA/2mice(12-15g)model[3]Dosage:0mg/kg,1mg/kg,3mg/kg,10mg/kgAdministration:p.o.,onceResult:Reducedtheincidenceofwild-runningandclonicseizures,andpreventedtonicseizuresandmortality.AnimalModel:MaleNMRImice(21-25g)model[3]Dosage:0mg/kg,10mg/kg,30mg/kg,100mg/kgAdministration:p.o.,onceResult:Prevented6-HzseizureswithanED50of13mg/kg.AnimalModel:STZ-induced(75mg/kg)CNPSDrats[4]Dosage:0.316,1.0,10mg/kgAdministration:p.o.,onceResult:Reducedmechanicalhyperalgesia.AnimalModel:SDratsmodel[4]Dosage:10mg/kgAdministration:p.o.,onceResult:Increasedthesynthesisofanti-hyperalgesicneurosteroids.4/5 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEAnimalModel:SeverecervicalspinalnervecompressioninjurySDratsmodel[4]Dosage:5mg/kg,10mg/kgAdministration:p.o.,onceResult:Hadneuroprotectiveandregenerativeeffects,acceleratedandimprovedfunctionalrecoveryaftertraumaticperipheralnerveinjury.REFERENCESMasegosaVM,etal.NovelDualMechanismGRT-XAgonistActingonKv7PotassiumChannel/TranslocatorProteinReceptorPreventsMotoneuronDegenerationFollowingExposuretoMouseandHumanAmyotrophicLateralSclerosis/FrontotemporalDementiaAstrocyte-ConditionedMedia.ACSChemNeurosci.