Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesKRASinhibitor-9Cat.No.:HY-137497CASNo.:300809-71-6分?式:C??H?ClN?S?分?量:292.81作?靶點:Ras;Apoptosis作?通路:GPCR/GProtein;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:250mg/mL(853.80mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.4152mL17.0759mL34.1518mL5mM0.6830mL3.4152mL6.8304mL10mM0.3415mL1.7076mL3.4152mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存?式和期限。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?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(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)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%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(7.10mM);Clearsolution此?案可獲得≥2.08mg/mL(7.10mM，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2.液中，混合均勻。請依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(7.10mM);Clearsolution1/3此?案可獲得≥2.08mg/mL(7.10mM，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KRASinhibitor-9有效的KRAS抑制劑(Kd=92μM)，阻?GTP-KRAS的形成和KRAS下游激活。KRASinhibitor-9以中等的結(jié)合親和?與KRASG12D，KRASG12C和KRASQ61H蛋?結(jié)合。KRASinhibitor-9導(dǎo)致G2/M細(xì)胞周期停滯并誘導(dǎo)凋亡(apoptosis)。KRASinhibitor-9選擇性抑制具有KRAS突變的NSCLC細(xì)胞的增殖，但不抑制正常肺細(xì)胞的增殖。KRASinhibitor-9體外研究KRASinhibitor-9boundtoKRASG12D,KRASG12CandKRASQ61Hproteinwithamoderatebindingaffinityof-5.38,-5.41,and-3.97kcal/mol,respectively[1].KRASinhibitor-9(0-100μM)showsstronginhibitionselectivityinNSCLCcellswithIC50srangingfrom39.56to66.02μMforH2122,H358andH460cells(at72hours)[1].KRASinhibitor-9(0-100μM;24hours)blocksGTP-KRASformationinH2122,H358andH460cells[1].KRASinhibitor-9(25-100μM;48hours)inhibitstheactivationofKRASdownstreamsignalingpathway[1].KRASinhibitor-9(0-100μM;24-72hours)inducescellcyclearrestandapoptosisinNSCLC[1].CellViabilityAssay[1]CellLine:H2122(KRASG12C),H358(KRASG12C)andH460(KRASQ61H)celllinesConcentration:0,25,50,100μMIncubationTime:24,48,and72hoursResult:InhibitedthreeNSCLCcelllinesinadose-andtime-dependentmanner,butnotinnormallungfibroblastcelllineCCD-19Lu.WesternBlotAnalysis[1]CellLine:H2122,H358andH460cellsConcentration:0,25,50,100μMIncubationTime:48hoursResult:ReducesthelevelsofphosphorylationofCRAFandAKTinadose-dependentmannerinH2122,H358andH460cells.ApoptosisAnalysis[1]CellLine:H2122,H358,H460cellsConcentration:0,25,50,100μM2/3IncubationTime:24-72hoursResult:SignificantlydecreasedinG0/G1phasewhileremarkablyincreasedinG2/Mphaseafter24hoursandinducedasignificantlyincreasedapoptosisfor48hinNSCLCcelllines.REFERENCES[1].XieC,etal.IdentificationofaNewPotentInhibitorTargetingKRASinNon-smallCellLungCancerCells.FrontPharmacol.2017;8:823.Published2017Nov14.McePdfH