KN-93-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEKN-93Cat.No.:HY-15465CASNo.:139298-40-1分⼦式:C₂₆H₂₉ClN₂O₄S分⼦量:501.04作⽤靶点:CaMK;Autophagy作⽤通路:NeuronalSignaling;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥50mg/mL(99.79mM)扫描⼆维码，*"≥"meanssoluble,butsaturationunknown.运⽤溶解⽅案计算器获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9958mL9.9792mL19.9585mL5mM0.3992mL1.9958mL3.9917mL10mM0.1996mL0.9979mL1.9958mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥0.83mg/mL(1.66mM);Clearsolution此⽅案可获得≥0.83mg/mL(1.66mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL8.3mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:0.83mg/mL(1.66mM);Clearsolution;Needultrasonicandwarming此⽅案可获得0.83mg/mL(1.66mM)的澄溶液。以1mL⼯作液为例，取100μL8.3mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥0.83mg/mL(1.66mM);Clearsolution此⽅案可获得≥0.83mg/mL(1.66mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL8.3mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性KN-93可渗透细胞，可逆和竞争性的抑制剂钙调蛋⽩依赖性激酶II型(CaMKII)抑制剂，Ki为370nM。IC50&TargetKi:370nM(CaMK)体外研究After2daysofKN-93treatment,95%ofcellsarearrestedinG1.G1arrestisreversible;1dayafterKN-93release,apeakofcellshadprogressedintoSandG2-M.KN-93alsoblockscellgrowthstimulatedbybasicfibroblastgrowthfactor,platelet-derivedgrowthfactor-BB,andepidermalgrowthfactorinNIH3T3fibroblasts[1].KN-93inhibitstheH+,K+-ATPaseactivitybutstronglydissipatestheprotongradientformedinthegastricmembranevesiclesandreducesthevolumeofluminalspace[2].KN-93(0.5μM)preventsincreasedLVdevelopedpressureduringactionpotentialprolongationandearlyafterdepolarizations.Ca2+-independentCaMkinaseactivityisincreasedduringearlyafterdepolarizationsandthisincreaseispreventedbyKN-93[3].KN-93(10μM)significantlyinhibitstheactivationofCaMKII/NF-κBsignalinginducedbyelevatedglucose,andsubsequentlydecreasestheexpressionofVEGF,iNOSandICAM-1inMüllercells[4].体内研究KN-93(1mg/kg/day,i.p.)inhibitsretinalvascularleakageinducedbydiabetes,andsuppressesphosphorylationofCaMKIIandNF-κBindiabeticretina[4].PROTOCOLCellAssay[4]Cellviabilityisassessedbythe3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)assay.Briefly,Müllercellsareseededatadensityof10×104cellsperwellin96-wellplatesandcultureduntilsub-confluence.Next,cellsaretreatedwithcurcuminfor24hbeforeincubationwithMTT(5mg/mL)at37°Cin5%CO2atmospherefor4h.Theculturemediumisthenremoved,andtheformazanformedinthereactionisdissolvedin150μLDMSO.Theopticaldensityofthesolutionismeasuredat490nmusingamultifunctionalmicroplatereader.Cellviabilityineachwellispresentedasapercentageofthecontrol(vehicle-treatedgroup).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMaleSprague-Dawleyrats(8weeksofage)weighing180-200gareusedinthisstudy.RatsarehousedinAdministration[4]ventilatedmicroisolatorcageswithfreeaccesstowaterandfood.TheratsarerandomLyassignedtoreceive2/4www.MedChemEwww.MedChemEeither60mg/kgSTZintraperitoneallyorcitratebufferalone.Ratsarecategorizedasdiabeticwhenbloodglucoselevelsexceeded16.7mMat48hafterSTZtreatment.Twoweeksaftertheinductionofdiabetes,ratsaredividedrandomLyintothreesubgroups:STZ-diabeticrats(n=12),STZ-treateddiabeticratsadministeredcurcumin(n=12),orSTZ-diabeticratsadministeredKN93(n=12)fora12-weekperiod.Curcuminissuspendedinsalinecontaining0.5%carboxymethylcelluloseataconcentrationof20mg/mLandadministeredviaoralgavageatatotaldoseof100mg/kg/day.KN93isadministeredbyintraperitonealinjectionat1mg/kg/day.ControlSTZ-treateddiabeticratsandnon-diabeticcontrols(n=12)aregavageadministeredsalinecontaining0.5%carboxymethylcelluloseonadailybasis.Bodyweightsandbloodglucoselevelsaremeasuredevery2weeks.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellSyst.2018Apr25;6(4):424-443.e7.•Diabetes.2018Sep;67(9):1748-1760.•SciTotalEnviron.2020Feb10;703:134702.•OxidMedCellLongev.2021Mar30.•OxidMedCellLongev.2019Dec7;2019:2193019.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TombesRM,etal.G1cellcyclearrestandapoptosisareinducedinNIH3T3cellsbyKN-93,aninhibitorofCaMK(themultifunctionalCa2+/CaMkinase).CellGrowthDiffer.1995Sep;6(9):1063-70.[2].MamiyaN,etal.InhibitionofacidsecretioningastricparietalcellsbytheCa2+/calmodulin-dependentproteinkinaseIIinhibitorKN-93.BiochemBiophysResCommun.1993Sep15;195(2):608-15.[3].AndersonME,etal.KN-93,aninhibitorofmultifunctionalCa++/calmodulin-dependentproteinkinase,decreasesearl