GSK235-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK235Cat.No.:HY-179625分⼦式:C₂₁H₃₀N₄O₃分⼦量:386.49作⽤靶点:Aminopeptidase作⽤通路:MetabolicEnzyme/Protease储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性GSK235⼀种⼝服有效的选择性变构内质⽹氨肽酶1(ERAP1)抑制剂，对⼈和⿏ERAP1的pIC50值分别为8.45和7.59。GSK235对两种同性最⾼的酶ERAP2和IRAP的选择性超过1000倍。GSK235可以调节癌细胞的免疫肽组，并增强癌细胞的抗原性。GSK235可⽤于结直肠癌和关节炎的研究。体外研究GSK235(compound21)(1μM,0.61μM;1hour,24h)demonstratespotentinhibitionofERAP1andERAAPwithhighselectivityinhumanandmouseenzymes[1].GSK235showsapIC50valueof7.25inHeLaantigenpresentationassay[1].GSK235(1µM;30days)affectsawidervarietyofimmunopeptidesinCT26tumorcells.Substantialevidenceofpeptidelengtheningwasobserved;forexample,significantincreasesin10-merand11-merpeptideswereaccompaniedbydecreasesin9-merand8-merpeptides[1].GSK235showsnoactivityagainstthehERGchannel[1].体内研究GSK235(compound21)(30,90,270mg/kg,oral,twicedaily,for17days)reducestumorgrowthandmodulatestheimmunopeptidomeinadose-dependentmannerintheCT26syngeneicmicemodel[1].GSK235(30,90,270mg/kg,oral,twicedaily;fromday18today36)reducesarthritisscoresandimmuneactivationinthecollagen-inducedarthritis(CIA)modelinadose-dependentmannerwithoutevidenceofautoimmuneexacerbation[1].AnimalModel:FemaleBALB/c(6-8weeksold)wereinoculatedsubcutaneouslyintherighthindflankwith5x104CT26cells[1]Dosage:30mg/kg,90mg/kg,270mg/kgAdministration:Oral;twicedaily(BID);for17days1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Observedwithsignificantreductionintumorvolumebyterminationofthestudy,day17,atthehighestdose(270mg/kg)andnosignificantdose-dependentbody-weightchangeswereobserved.AnimalModel:MaleDBA/1OlaHsd(6-7weeksold)(Collagen-inducedarthritis(CIA)model)[1]Dosage:30mg/kg,90mg/kg,270mg/kgAdministration:Oral;twicedaily(BID);fromday18today36Result:Showedadose-dependentreductioninarthritisscores,withthehighestdose(270mg/kg)achievingareductioncomparabletotheTNFinhibitorEnbrel.Alsoreducedanti-collagentypeIIIgGlevels,IL-12p40,andIL-6levels,anddecreasedMHC-IexpressiononBcellsandcDCs.Noexacerbationofautoimmuneresponseswasobserved.REFERENCES[1].ChristopherP.Tinworth,etal.DiscoveryofanorallyavailablepotentERaminopeptidase1(ERAP1)inhibitorthatenhancesanti-tumorresponsesandlimitsinflammatoryautoimmunityinvivo.bioRxiv.November17,2025.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplica