DC-PGKI-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDC-PGKICat.No.:HY-177944CASNo.:2829198-49-2分⼦式:C₂₆H₂₉Cl₂N₇O₃分⼦量:558.46作⽤靶点:PhosphoglycerateKinase(PGK);Keap1-Nrf2;InterleukinRelated作⽤通路:MetabolicEnzyme/Protease;NF-κB;Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性DC-PGKI⼀种⼝服有效的ATP竞争性PGK1抑制剂(IC50=0.16μM，Kd=99.08nM)。DC-PGKI在体外和体内均能稳定PGK1，并抑制糖酵解活性和PGK1的激酶功能。DC-PGKI介导的PGK1抑制导致NRF2(核因⼦-红细胞因⼦2相关因⼦2，NFE2L2)的积累，NRF2随后转位⾄细胞核，与IL-1β和IL-6因的近端区域结合，并抑制LPS诱导的这些因的表达。DC-PGKI可⽤于结肠炎的研究[1]。IC50&TargetPGK1PGK1IL-6IL-1β0.16μM(IC50)99.08nM(Kd)体外研究DC-PGKI(0.1-30μM,3h)canincreaseRAW264.7cells'PGK1thermalstabilityinaconcentration-dependentmanner[1].DC-PGKI(5-10μM,10h)inhibitsPGK1glycolyticmetabolicactivityintherestingandactivatedinRAW264.7cells[1].DC-PGKI(10-20μM)notablydecreasestheSer30phosphorylationlevelofBeclin1inRAW246.7cells,indicatingthatDC-PGKIalsoimpairsPGK1’skinasefunction[1].DC-PGKI(5-20μM)inhibitsLPS-inducedIL-1βandIL-6mRNAinaconcentration-dependentmannerinRAW246.7cells[1].DC-PGKI(0-20μM)significantlyinhibitsLipopolysaccharides(HY-D1056)(LPS)-inducedprecursorofIL-1βandIL-6inRAW264.7cells[1].DC-PGKI(5-20μM,7h)resultsinasignificantreductioninKEAP1proteinlevel,accumulationofNRF2,aswellasupregulationofboththemRNAandproteinlevelsofHMOX1inLPS-inducedRAW264.7cells[1].DC-PGKI(5-20μM,7h)upregulatesotherdownstreamtargetgenesofNRF2,includingTxnrd1,Prdx1,Gclc,Sod1,Fth1,andEphx1,inbothLPS-treatedanduntreatedconditionsinRAW264.7cells[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEWesternBlotAnalysis[1]CellLine:RAW264.7cellsConcentration:0μM,0.1μM,0.5μM,1μM,5μM,10μM,20μM,30μMIncubationTime:3hResult:IncreasedRAW264.7cells'PGK1thermalstabilityinaconcentration-dependentmanner.RealTimeqPCR[1]CellLine:RAW264.7cellswerestimulatedwithLPS(1μg/mL)for4hours.Concentration:5μM,10μM,20μMIncubationTime:7hResult:InhibitedthemRNAexpressionofIL-1βandIL-6.ResultedinasignificantreductioninKEAP1proteinlevel,accumulationofNRF2,aswellasupregulationofboththemRNAandproteinlevelsofHMOX1.UpregulatedotherdownstreamtargetgenesofNRF2,includingTxnrd1,Prdx1,Gclc,Sod1,Fth1,andEphx1.体内研究DC-PGKI(5-10mg/kg,p.o.,oncedailyfor8days)significantlyalleviatesdextransulfatesodium(DSS)-inducedcolitissymptomsinmicebyinhibitingPGK1andactivatingtheNRF2pathway[1].AnimalModel:8-week-oldC57BL/6malemiceweregiven5%(w/v)DSSfor7daystoinduceacutecolitis,followedbydrinkingwaterforoneday[1].Dosage:5mg/kg,10mg/kgAdministration:P.o.,oncedailyfor8daysResult:SignificantlyreducedweightlossinducedbyDSS.Thediseaseactivityindex(DAI)decreasedcomparedtotheDSSgroup.Reducedcolonictissuedamage,lymphocyteinfiltration,andcryptdestruction.LoweredserumandtissueproteinandmRNAlevelsofIL-1βandIL-6.IncreasedNRF2proteinaccumulationincolonictissue.REFERENCES[1].LiaoL,etal.ApotentPGK1antagonistrevealsPGK1regulatestheproductionofIL-1βandIL-6.ActaPharmSinB.2022Nov;12(11):4180-4192.McePdfHeight2/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemECaution:Producthasnotb