LUF7996-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemELUF7996Cat.No.:HY-180571CASNo.:3104736-80-0分⼦式:C₃₉H₃₄Cl₂F₃N₅O₈S分⼦量:860.68作⽤靶点:PROTACs;CCR作⽤通路:PROTAC;GPCR/GProtein;Immunology/Inflammation储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性LUF7996⼀种靶向CCR2PROTAC降解剂可降解CCR2且DC50为2.6μM。LUF7996能够同时结合CCR2与E3连接酶cereblon，并呈现出持续且浓度依赖性的CCR2降解作⽤。LUF7996依赖于溶酶体途径来诱导CCR2降解，并在体外有效抑制单核细胞的迁移[1]。IC50&TargetCCR22.6μM(DC50)体外研究LUF7996(compound10)(10μM)displaces[3H]CCR2-RA-[R]withpKi=6.9nManddisplays<50%inhibitoninU2OS-CCR2cells[1].LUF7996(0.1-31.6μM,2h)notdisplayanysubstantialdegradativecapacitywhentestedatconcentrationsbelow1μM,hasarapidandconcentration-dependentdegradationofCCR2withDC50=5.6μMwithoutindicationofahookeffectatconcentrationshigherthan1μM,Dmax=85%at31.6μMandDmax=79%at10μMinHEK293-LgBiTcells[1].LUF7996bindsCCR2withIC50=7.858μM,exhibitsthestrongestCRBNengagementwithIC50=143μM[1].LUF7996(10μM,12or24h)mediatedCCR2degradationisrescueduponcotreatmentwitheitheraCRBNinhibitor(competingforthebindingpocket)oraCRBNdegrader[1].LUF7996(10μM,3h)resultasignificantincreaseinCCR2ubiquitination,degradesCCR2leastpartiallythroughCRBNandubiquitin-dependentmechanisms[1].LUF7996(10μM,0-25h)didnotblockCCR2degradationbutenhancesCCR2degradationafter16hwhencotreatwithproteasomeinhibitorsBortezomib(HY-10227)orMG-132(HY-13259)(10μM)ortheneddylationinhibitorMLN-4924(HY-70062)(250nM),suggestingaproteasome-andneddylation-independentmechanismofaction[1].1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemELUF7996(10μM,0-25h)hasCCR2degradativeeffectbutpreventedbyinhibitionofthelysosomalpathway,asevidencedbythefullrestorationofCCR2levelswithBaf-A1(HY-100558)andthedecreaseddegradationobservedwithChloroquine(HY-17589A)[1].LUF7996(10μM,24h)resultsasignificantreductionin[3H]CCR2-RA-[R]bindinginTHP-1cells,indicatingareductionofCCR2levels[1].LUF7996(10μM)demonstrates84%potentinhibitionofCCL2-inducedmonocytemigrationinTHP-1cells[1].REFERENCES[1].EssaK,etal.LeveragingTargetedProteinDegradationforGProtein-CoupledReceptors:TheDevelopmentofCCR2MolecularDegraders.JMedChem.2025Dec25;68(24):26525-26546.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.For