Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesNAE-IN-M22Cat.No.:HY-115537CASNo.:864420-54-2分?式:C??H??Cl?N?分?量:363.32作?靶點:Apoptosis作?通路:Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:250mg/mL(688.10mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.7524mL13.7620mL27.5239mL5mM0.5505mL2.7524mL5.5048mL10mM0.2752mL1.3762mL2.7524mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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?；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的?式助溶1.請依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(5.72mM);Clearsolution此?案可獲得≥2.08mg/mL(5.72mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲備液加到400μLPEG300中，混合均勻；向上述2.體系中加?50μLTween-80，混合均勻；然后繼續加?450μL?理鹽?定容?1mL。請依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.72mM);Clearsolution1/3此?案可獲得≥2.08mg/mL(5.72mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(5.72mM);Clearsolution此?案可獲得≥2.08mg/mL(5.72mM，飽和度未知)的澄溶液，此?案不適?于實驗周期在半個?以上的實驗。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性NAE-IN-M22?種有效，選擇性和可逆的NEDD8活化酶(NAE)抑制劑，效?在微爾范內。NAE-IN-M22抑制多種癌細胞?長并誘導A549細胞凋亡。NAE-IN-M22還可以在體內抑制腫瘤的?長。IC50&TargetNEDD8activatingenzyme(NAE)[1]體外研究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.體內研究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