KU-60019-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEKU-60019Cat.No.:HY-12061CASNo.:925701-46-8分⼦式:C₃₀H₃₃N₃O₅S分⼦量:547.67作⽤靶点:ATM/ATR作⽤通路:CellCycle/DNADamage;PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(182.59mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.8259mL9.1296mL18.2592mL5mM0.3652mL1.8259mL3.6518mL10mM0.1826mL0.9130mL1.8259mL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；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。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%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(4.56mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.56mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性KU-60019⼀种ATM激酶特异性的抑制剂，IC50为6.3nM。IC50&TargetATMDNA-PKcs6.3nM(IC50)1.7μM(IC50)体外研究KU-60019isanimprovedanalogueofKU-55933.KU-55933hasanIC50of13nMandKiof2.2nMinvitroandishighlyspecificfortheATMkinaseusingapanelof60proteinkinases.KU-60019isanimprovedinhibitoroftheATMkinasewithanIC50of6.3nM,approximatelyhalfthatofKU-55933.TheIC50valuesforDNA-PKcsandATRare1.7and>10μM,respectively,almost270-and1600-foldhigherthanforATM.KU-60019is10-foldmoreeffectivethanKU-55933atblockingradiation-inducedphosphorylationofkeyATMtargetsinhumangliomacells.InhumanU87gliomacells,KU-55933completelyinhibitsphosphorylationofp53(S15)at10μMbutnotat3μM,whereasγ-H2AXlevelsareonlypartlyreducedwith10μM1hafterirradiation.Bycomparison,3μMKU-60019completelyinhibitsp53phosphorylationandpartialinhibitsat1μM[1].体内研究DespitePTEN-deficientcontroltumorsreachinga4-foldincreaseinsizebeforePTENwild-typecontrols,KU-60019-treatedPTEN-deficienttumorsdisplayastatisticallysignificantslowingingrowth.Thisgrowthinhibitionisespeciallyevidentatthestartoftheexperiment(days5-12)justafterKU-60019isadministered(days1-5)[2].PROTOCOLCellAssay[1]CellgrowthisdeterminedbyAlamarBlue.U1242cellsareseriallydiluted,allowedtoattachfor6handthenexposedtoKU-60019at3μM.Atdays1,3and5afterseeding,AlamarBlueisaddedtothemediumtotherecommendedfinalconcentration.Platesareincubatedfor1hat37°CandfluorescencedeterminedonaFluoroCountplatereader(excitation530nm,emission590nm)andvaluestakenasameasureofcellgrowth[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]Cells(3×107)areimplantedintomaleFoxChaseSevereCombinedImmunodeficiency(SCID)mice.AdministrationofDoxycyclineisstartedwhentumorsreach100mm3involumeandisperformedevery48hoursuptoremovaloftheanimalfromtheexperiment.Forty-eighthoursafterPTENinduction,animalsareadministeredKU-60019(100mg/kg)for5consecutivedaysandmeasureduntiltheyreachatarget400mm3volume.Measurementsoftumorvolumeandbodyweighttookplaceevery3daysusingcalipers.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•ActaBiomater.2021Mar31;S1742-7061(21)00201-4.•CellRep.2020Jan14;30(2):497-509.e4.•OxidMedCellLongev.2022Jun24;2022:4201287.•ActaPharmacolSin.2021Jan7.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GoldingSE,etal.ImprovedATMkinaseinhibitorKU-60019radiosensitizesgliomacells,compromisesinsulin,AKTandERKprosurvivalsignaling,andinhibitsmigrationandinvasion.MolCancerTher.2009Oct;8(10):2894-902.[2].McCabeN,etal.MechanisticRationaletoTargetPTEN-DeficientTumorCellswithInhibitorsoftheDNADamageResponseKinaseATM.CancerRes.2015Jun1;75(11):215