CLK1-IN-1-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECLK1-IN-1Cat.No.:HY-103082CASNo.:2123491-32-5分⼦式:C₂₄H₁₆FN₅O分⼦量:409.42作⽤靶点:CDK作⽤通路:CellCycle/DNADamage储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:25mg/mL(61.06mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4425mL12.2124mL24.4248mL5mM0.4885mL2.4425mL4.8850mL10mM0.2442mL1.2212mL2.4425mL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>>90%cornoilSolubility:≥2.5mg/mL(6.11mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性CLK1-IN-1⼀个有效的、Cdc2-like激酶(CLK1)的选择性抑制剂，其IC50值为2nM。IC50&TargetCLK12nM(IC50)体外研究CLK1isthemostpotentlyinhibitedkinase(IC50:2nM).InadditiontoCLK1,onlytwokinaseshaveanIC50valuelessthan100nM,namelyCLK2(IC50:31nM)andCLK4(IC50:8nM),DYRK1Aisthestrongestoff-target.TheabilityofCLK1-IN-1toinduceautophagyinBNLCL.2andSKOV-3(humanovariancancercellline)cellsisalsoexamined.TheeffectsofCLK1-IN-1onyellowLC3punctaalsodisplaysobviousdosedependency,andadoseof10μMshowsthebestperformance.Inaddition,inCLK1-IN-1-treatedcells,thenumberofredLC3puncta(mRFPsignalsonly35)increasescomparedwiththatofDMSO-treatedcells,indicatingtheformationofautolysosomes.Importantly,CLK1-IN-1stimulatsthedegradationofSQSTM1/p62andincreasestheratioofredLC3punctatoyellowLC3puncta,bothofwhichindicateaninductionofautophagicfluxbyCLK1-IN-1[1].体内研究APAPexposureresultsinsevereliverinjury,andtreatmentwithCLK1-IN-1(ip,30mg/kg)impartsasignificanthepatoprotectiveeffect.TheresultsshowthattreatmentwithCLK1-IN-1decreasesserumALTandASTlevelssignificantlysuchthatbothmarkerenzymesreturntonormallevels[1].PROTOCOLCellAssay[1]BNLCL.2(mouseembryoniclivercellline)isselected,andthreeconcentrations(20nM,100nM,and10μM)ofCLK1-IN-1areused[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Drug-inducedliverinjury(DILI)isamajorpublichealthconcernandaccountsformorethan50%ofacuteliverfailurecases.APAPisawidelyusedantipyreticanalgesicdrug.Herein,theAPAP-inducedhepatotoxicitymousemodelisusedtoexaminethetherapeuticeffectofCLK1-IN-1invivo.MaleC57BL/6micearegiveneithersaline(n=3,ip)orAPAP(500mg/kg)(n=15,ip).Toexaminethehepatoprotectiveeffect,miceareinjected(ip)withCLK1-IN-1(25)(30mg/kg),30(30mg/kg,positivecontrol),rapamycin(30mg/kg,positivecontrol),orsolvent(12.5%ethanoland12.5%castoroil,10mL/kg),immediatelyfollowedbyAPAP(500mg/kg)injection(ip).Allmicearesacrificed6hlater.LiversectionsareexaminedbyH&Estaining,andtheserumfromthebloodsamplesisusedforALTandASTactivitytests[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].SunQZ,etal.DiscoveryofPotentandSelectiveInhibitorsofCdc2-LikeKinase1(CLK1)asaNewClassofAutophagyInducers.JMedChem.2017Jul27;60(14):6337-6352.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMcePdfHeightCaution:Product