Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECLK1-IN-1Cat.No.:HY-103082CASNo.:2123491-32-5分?式:C??H??FN?O分?量:409.42作?靶點:CDK作?通路:CellCycle/DNADamage儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(61.06mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4425mL12.2124mL24.4248mL5mM0.4885mL2.4425mL4.8850mL10mM0.2442mL1.2212mL2.4425mL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；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。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%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.11mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性CLK1-IN-1?個有效的、Cdc2-like激酶(CLK1)的選擇性抑制劑，其IC50值為2nM。IC50&TargetCLK12nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEMcePdfHeightCaution:Product