KN-93-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEKN-93Cat.No.:HY-15465CASNo.:139298-40-1分?式:C??H??ClN?O?S分?量:501.04作?靶點(diǎn):CaMK;Autophagy作?通路:NeuronalSignaling;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥50mg/mL(99.79mM)掃描?維碼，*"≥"meanssoluble,butsaturationunknown.運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9958mL9.9792mL19.9585mL5mM0.3992mL1.9958mL3.9917mL10mM0.1996mL0.9979mL1.9958mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶1.請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥0.83mg/mL(1.66mM);Clearsolution此?案可獲得≥0.83mg/mL(1.66mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL8.3mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:0.83mg/mL(1.66mM);Clearsolution;Needultrasonicandwarming此?案可獲得0.83mg/mL(1.66mM)的澄溶液。以1mL?作液為例，取100μL8.3mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥0.83mg/mL(1.66mM);Clearsolution此?案可獲得≥0.83mg/mL(1.66mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL8.3mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性KN-93可滲透細(xì)胞，可逆和競(jìng)爭(zhēng)性的抑制劑鈣調(diào)蛋?依賴性激酶II型(CaMKII)抑制劑，Ki為370nM。IC50&TargetKi:370nM(CaMK)體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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