Featured Publications
Catalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson DP, Mares A, Smith IE, Ko E, Campos S, Miah AH, Mulholland KE, Routly N, Buckley DL, Gustafson JL, Zinn N, Grandi P, Shimamura S, Bergamini G, Faelth-Savitski M, Bantscheff M, Cox C, Gordon DA, Willard RR, Flanagan JJ, Casillas LN, Votta BJ, den Besten W, Famm K, Kruidenier L, Carter PS, Harling JD, Churcher I, Crews CM. Catalytic in vivo protein knockdown by small-molecule PROTACs. Nature Chemical Biology 2015, 11: 611-617. PMID: 26075522, PMCID: PMC4629852, DOI: 10.1038/nchembio.1858.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBinding SitesBiocatalysisBreast NeoplasmsFemaleHumansMCF-7 CellsMiceModels, MolecularMolecular Targeted TherapyNeoplasm ProteinsNeoplasm TransplantationProteasome Endopeptidase ComplexProtein BindingProteolysisReceptor-Interacting Protein Serine-Threonine Kinase 2Receptors, EstrogenSmall Molecule LibrariesUbiquitinUbiquitinationVon Hippel-Lindau Tumor Suppressor Protein
2024
Development of Ligands and Degraders Targeting MAGE-A3
Li K, Krone M, Butrin A, Bond M, Linhares B, Crews C. Development of Ligands and Degraders Targeting MAGE-A3. Journal Of The American Chemical Society 2024, 146: 24884-24891. PMID: 39190582, DOI: 10.1021/jacs.4c05393.Peer-Reviewed Original ResearchDNA-encoded librariesSmall molecule ligandsDevelopment of ligandsE3 ligase complexCocrystal structureChemical matterLigandPROTAC moleculesSmall moleculesLigase complexTargeted protein degradationMAGE-A3Substrate recognition moduleType I MAGEsRING E3 ligasesMoleculesCancer-selective expressionDimer interfaceImprove immunotherapy outcomesIncreased antigen presentationHigh tumor gradeE3 ligaseComplexBiochemical functionsCancer cell surface
2022
Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation
Nalawansha DA, Li K, Hines J, Crews CM. Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation. Journal Of The American Chemical Society 2022, 144: 5594-5605. PMID: 35311258, PMCID: PMC10331457, DOI: 10.1021/jacs.2c00874.Peer-Reviewed Original ResearchConceptsE3 ligase complexLigase complexProtein degradationReader proteinsMethyl readersE3 ligaseProteasomal degradationPROTAC designProtein levelsProteinLigand pairsDrug discovery paradigmPROTACsNatural mechanismGeneralizable approachComplexesDiscovery paradigmCUL4BRD2DegradationLigaseL3MBTL3FKBP12Biological evaluationPromising strategy