NAE-IN-M22-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrariesNAE-IN-M22Cat.No.:HY-115537CASNo.:864420-54-2分⼦式:C₂₀H₂₄Cl₂N₂分⼦量:363.32作⽤靶点:Apoptosis作⽤通路:Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(688.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.7524mL13.7620mL27.5239mL5mM0.5505mL2.7524mL5.5048mL10mM0.2752mL1.3762mL2.7524mL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:≥2.08mg/mL(5.72mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.72mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述2.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。请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.72mM);Clearsolution1/3此⽅案可获得≥2.08mg/mL(5.72mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL20.8mg/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:≥2.08mg/mL(5.72mM);Clearsolution此⽅案可获得≥2.08mg/mL(5.72mM，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100μL20.8mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性NAE-IN-M22⼀种有效，选择性和可逆的NEDD8活化酶(NAE)抑制剂，效⼒在微尔范内。NAE-IN-M22抑制多种癌细胞⽣长并诱导A549细胞凋亡。NAE-IN-M22还可以在体内抑制肿瘤的⽣长。IC50&TargetNEDD8activatingenzyme(NAE)[1]体外研究M22(0.37-90μM;24h)blocksneddylationpathwayselectivelyandsuppressesdegradationofCRLsubstratesinA549cells[1].M22(0.1-100μM;48h)inhibitsA549cellproliferationcompletelyat30µM(GI50=5.5µM,GI90=19.3µM)[1].M22(15-30μM;36h)promotesapoptosisinA549cellline[1].CellViabilityAssay[1]CellLine:A549cellsConcentration:0.37,1.11,3.33,10,30,90μMIncubationTime:24hoursResult:InhibitedformationsofUba3-NEDD8andUbc12-NEDD8.ResultedinacorrespondingdecreaseintheabundanceofCullins-NEDD8.Decreasedthedegradationsofp27andCDT1.Preventedp53fromdegradation.体内研究M22(60mg/kg;i.p.oncedailyfor14d)inhibitstumorgrowthinnudemicebearingAGSxenografts[1].M22(0.36-90μM)haslowacutetoxicityinzebrafishmodel[1].REFERENCES[1].LuP,et,al.DiscoveryofanovelNEDD8ActivatingEnzymeInhibitorwithPiperidin-4-amineScaffoldbyStructure-BasedVirtualScreening.ACSChemBiol.2016Jul15;11(7):1901-7.McePdfHeight2/3MedChemExpress(MCE)只