CDK8-IN-11-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECDK8-IN-11Cat.No.:HY-151463分⼦式:C₁₉H₁₅F₃N₄O₂分⼦量:388.34作⽤靶点:CDK;β-catenin作⽤通路:CellCycle/DNADamage;StemCell/Wnt储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性CDK8-IN-11⼀种有效的、选择性的CDK8抑制剂，IC50值为46nM。CDK8-IN-11可抑制WNT/β-catenin信号通路。CDK8-IN-11可⽤于结肠癌的研究。IC50&TargetCDK846nM(IC50)体外研究CDK8-IN-11(compound29,200nM)showsinhibitoryeffectsagainstCDK8by73.6%[1].CDK8-IN-11(0-50μM,48h)inhibitscellproliferationinHCT-116,HHT-29,SW480,CT-26,GES-1cells[1].CDK8-IN-11(0-4μM,48h)inhibitsthephosphorylationofSTAT1atSer727mediatedbyCDK8inHCT-116cells[1].CDK8-IN-11(0-4μM,24h)suppressescanonicalWNT/β-cateninsignalingpathwaysandderegulatesβ-catenin-mediatedtranscriptioninHCT-116cells[1].CDK8-IN-11(0.5-2μM,48h)increasesthenumberofcellsintheG1phaseinHCT-116cells[1].CDK8-IN-11(0-4μM)reversesSorafenib(HY-10201)resistanceofHCT-116cells[1].CellProliferationAssay[1]CellLine:HCT-116,HHT-29,SW480,CT-26,GES-1cellsConcentration:0.08,0.4,2,10,and50μMIncubationTime:48hResult:InhibitedcellproliferationwithIC50valuesof1.2,0.7,2.4,5.5,62.7nMrespectively.WesternBlotAnalysis[1]1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECellLine:HCT-116cellConcentration:0,1,2,4μMIncubationTime:48hResult:InhibitedthephosphorylationofSTAT1atSer727withoutaffectingtheJAK-regulatedphosphorylationatTyr701.CellCycleAnalysis[1]CellLine:HCT-116cellConcentration:0.5-2μMIncubationTime:48hResult:IncreasedthenumberofcellsintheG1phasewithanobviousdecreasedpercentageofcellsintheG2/MandSphaseinHCT-116cells.体内研究CDK8-IN-11(compound29,10and40mg/kg,p.o.)inhibitstumorgrowthinCT-26xenograftmice[1].CDK8-IN-11(1000mg/kg,oralgavage,ICRmice)showsnoobviousabnormalbehaviorwithin7days[1].CDK8-IN-11(10mg/kg,p.o.;2mg/kg,i.v.,rats)showsmoderatepermeabilitywithanapparentpermeabilitycoefficientvalueof1.8×10−6cm/s[1].AnimalModel:CT-26xenograftmice[1]Dosage:10and40mg/kgAdministration:Oraladminstration(p.o.)Result:Reducedthetumorvolume,reducedβ-cateninandc-Myclevelintumor.AnimalModel:Rats(pharmacokineticassay)[1]Dosage:10mg/kg(p.o.),2mg/kg(i.v.)Administration:Oraladminstration(p.o.)orintravenousinjection(i.v.)Result:PharmacokineticprofileofCDK8-IN-11(compound29).dose(mg/kg)T1/2(h)Tmax(h)Cmax(ng/mL)F(%)10(p.o.)1.10.845331.72(i.v.)0.5318REFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].YaoYaoYan,etal.DesignandSynthesisofa2-Amino-pyridineDerivativeasaPotentCDK8InhibitorforAnti-colorectalCancerTherapy.JMedChem.2022Sep20.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedi