CI-1040-PD-184352-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECI-1040Cat.No.:HY-50295CASNo.:212631-79-3Synonyms:PD184352分⼦式:C₁₇H₁₄ClF₂IN₂O₂分⼦量:478.66作⽤靶点:MEK;Apoptosis作⽤通路:MAPK/ERKPathway;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(208.92mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0892mL10.4458mL20.8917mL5mM0.4178mL2.0892mL4.1783mL10mM0.2089mL1.0446mL2.0892mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.22mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.35mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CI-1040(PD184352)有⼝服活性，⾼度特异的MEK⼩分⼦抑制剂，对MEK1的IC50值为17nM。IC50&TargetMEK117nM(IC50)体外研究CI-1040directlyinhibitsMEK1withanIC50of17nM.IthasalsobeenshowntohavelittleactivityagainstapanelofrelatedkinaseswithIC50valuesmorethan2.5ordersofmagnitudehigher.TreatmentofwholecellswithCI-1040completelyinhibitsthemitogen-stimulatedphosphorylationofERK.CI-1040ataconcentrationof1μMisfoundtoinhibitphosphorylationofERK1andERK2by99%and92%,respectivelyinMDA-MB-231breastcancercells[1].CI-1040inducesapoptosisandinhibitsproliferationinU-937cellsinadoseandtime-dependentmanner.CI-1040inducesasignificantincreaseinPUMAmRNAandproteinlevels[2].体内研究ThesystemicadministrationoftheMEKinhibitorCI-1040reducesadenomaformationtoathirdandsignificantlyrestoreslungstructure.TheproliferationrateoflungcellsofmicetreatedwithCL-1040isdecreasedwithoutanyobviouseffectsondifferentiationofpneumocytes[3].PROTOCOLCellAssay[2]TheMEKinhibitorCI-1040isdissolvedinDMSOas10mMstocksolutionsandusedincellcultureatfinalconcentration50mg/mL.U-937cellsarepretreatedfor24hrswith5and20uMCI-1040,thentransfectedwithwt-p53siRNAorPUMAsiRNAfor48hrs.Then20mLofMTTsolutionareaddedtoeachwellandincubatedfurtherfor2hours.Upontermination,thesupernatantisaspiratedandtheMTTformazanformedbymetabolicallyviablecellsisdissolvedin100mLofisopropanol.Theplatesaremixedfor30minutesonagyratoryshaker,andabsorbanceismeasuredat595nmusingaplatereader[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:ThelungcancermousemodelisgeneratedbytargetingconstitutivelyactiveC-Rafkinasetothelung.Administration[3]BAY43-9006orCI-1040isdailyintraperitonealinjectedatadoseof100mg/kgfrom4monthsofageoveraperiodof21days.Lungswereisolatedandanalyzedattheendofthetreatmentperiod[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•ClinCancerRes.2020Apr15;26(8):2011-2021.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•Glia.2019Jul;67(7):1320-1332.•IntJBiolMacromol.2020May1;150:261-280.•IntJBiolMacromol.2018Dec;120(PtA):1039-1047.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].AllenLF,etal.CI-1040(PD184352),atargetedsignaltransductioninhibitorofMEK(MAPKK).SeminOncol.2003Oct;30(5Suppl16):105-16.[2].WeiCR,etal.MEKinhibitorCI-1040inducesapoptosisinacutemyeloidleukemiacellsinvitro.EurRevMedPharmacolSci.2016May;20(10):1961-8.[3].KramerBW,etal.UseofmitogeniccascadeblockersfortreatmentofC-Rafinducedlungadenomainvivo:CI-1040stronglyreducesgrowthandimproveslungstructure.BMCCancer.2004Jun1;4:24.Mc