Featured Publications
Induced protein degradation: an emerging drug discovery paradigm
Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nature Reviews Drug Discovery 2016, 16: 101-114. PMID: 27885283, PMCID: PMC5684876, DOI: 10.1038/nrd.2016.211.Peer-Reviewed Original ResearchConceptsProteolysis-targeting chimaerasProtein degradationUndruggable proteomeTarget protein degradationDifferent E3 ligasesInhibitor-based approachE3 ligasesDrug discovery platformProtein targetsProteomeDiscovery platformProtein expressionDrug discovery paradigmInhibition approachCell culturesDiscovery paradigmLigasesExact mechanismDegradationMouse modelDegradersProteinChimaerasPicomolar potency
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
2013
From epoxomicin to carfilzomib : chemistry, biology, and medical outcomes
Kim KB, Crews CM. From epoxomicin to carfilzomib : chemistry, biology, and medical outcomes. Natural Product Reports 2013, 30: 600-604. PMID: 23575525, PMCID: PMC3815659, DOI: 10.1039/c3np20126k.Peer-Reviewed Original ResearchMeSH KeywordsBiological ProductsDrug DiscoveryMolecular StructureMultiple MyelomaOligopeptidesProteasome InhibitorsConceptsActive natural productsNatural productsNatural product-based drug discoveryAnti-tumor natural productParent lead compoundRational drug designUnprecedented selectivityHigh-throughput screeningPeptide structureMolecular probesImproved activityDrug designLead compoundsDrug discoveryPharmacophoreEpoxyketonesChemistryProductsSelectivityCompoundsTherapeutic agentsBiological processesDiscoveryScaffoldsBristol-Myers Squibb
2012
Greasy tags for protein removal
Neklesa TK, Crews CM. Greasy tags for protein removal. Nature 2012, 487: 308-309. PMID: 22810693, DOI: 10.1038/487308a.Peer-Reviewed Original Research