KRAS-inhibitor-9-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrariesKRASinhibitor-9Cat.No.:HY-137497CASNo.:300809-71-6分⼦式:C₁₃H₉ClN₂S₂分⼦量:292.81作⽤靶点:Ras;Apoptosis作⽤通路:GPCR/GProtein;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(853.80mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.4152mL17.0759mL34.1518mL5mM0.6830mL3.4152mL6.8304mL10mM0.3415mL1.7076mL3.4152mL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%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(7.10mM);Clearsolution此⽅案可获得≥2.08mg/mL(7.10mM，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2.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.08mg/mL(7.10mM);Clearsolution1/3此⽅案可获得≥2.08mg/mL(7.10mM，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KRASinhibitor-9有效的KRAS抑制剂(Kd=92μM)，阻⽌GTP-KRAS的形成和KRAS下游激活。KRASinhibitor-9以中等的结合亲和⼒与KRASG12D，KRASG12C和KRASQ61H蛋⽩结合。KRASinhibitor-9导致G2/M细胞周期停滞并诱导凋亡(apoptosis)。KRASinhibitor-9选择性抑制具有KRAS突变的NSCLC细胞的增殖，但不抑制正常肺细胞的增殖。KRASinhibitor-9体外研究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