2021
BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma
Fiskus W, Mill CP, Perera D, Birdwell C, Deng Q, Yang H, Lara BH, Jain N, Burger J, Ferrajoli A, Davis JA, Saenz DT, Jin W, Coarfa C, Crews CM, Green MR, Khoury JD, Bhalla KN. BET proteolysis targeted chimera-based therapy of novel models of Richter Transformation-diffuse large B-cell lymphoma. Leukemia 2021, 35: 2621-2634. PMID: 33654205, PMCID: PMC8410602, DOI: 10.1038/s41375-021-01181-w.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBiomarkers, TumorBridged Bicyclo Compounds, HeterocyclicCell ProliferationCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansLymphoma, Large B-Cell, DiffuseMicePiperidinesProteinsProteolysisSulfonamidesTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsLarge B-cell lymphomaB-cell lymphomaRichter transformationBET protein inhibitorLymphoma burdenImproved survivalCombination therapyC-Myc levelsEffective therapyNovel therapiesCell lymphomaXenograft modelProtein inhibitorTherapyBET inhibitorsProtein expressionCLLGenetic alterationsLymphomaInhibitorsIRF4Single-cell RNA-seqHuman modelCRISPR knockoutCellsMajor advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs
Alabi SB, Crews C. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. Journal Of Biological Chemistry 2021, 296: 100647. PMID: 33839157, PMCID: PMC8131913, DOI: 10.1016/j.jbc.2021.100647.Peer-Reviewed Original ResearchConceptsProtein degradationProtein degradation pathwaysProteolysis targeting chimera (PROTAC) technologyUbiquitin-proteasome systemEndo-lysosomal pathwaySmall molecule inhibitorsDruggable spaceChemical toolsInnovative chemical toolMolecular glueChimera technologyProtein moleculesDegradation pathwayOutstanding questionsCurrent understandingMajor advancesPathwayAutophagyPROTACsDegradationCellsInhibitorsAdvances
2001
The ubiquitin‐proteasome pathway and proteasome inhibitors
Myung J, Kim K, Crews C. The ubiquitin‐proteasome pathway and proteasome inhibitors. Medicinal Research Reviews 2001, 21: 245-273. PMID: 11410931, PMCID: PMC2556558, DOI: 10.1002/med.1009.Peer-Reviewed Original ResearchConceptsUbiquitin-proteasome pathwayComplex biochemical machineryHuman diseasesDiverse cellular processesImportant cellular substratesMajor cellular networksCellular processesBiochemical machineryProtein degradationNatural proteasome inhibitorsCellular substratesCentral playerIntracellular processesMode of actionProteasome inhibitorsPathwayMolecular probesInhibitorsPotential therapeutic agentProteasomeImportant componentMachineryRegulationTherapeutic agentsLack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors
Myung J, Kim K, Lindsten K, Dantuma N, Crews C. Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors. Molecular Cell 2001, 7: 411-420. PMID: 11239469, DOI: 10.1016/s1097-2765(01)00188-5.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsBinding SitesCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesEndopeptidasesEpoxy CompoundsHumansHydrolysisKetonesKineticsModels, BiologicalMultienzyme ComplexesProtease InhibitorsProteasome Endopeptidase ComplexProtein SubunitsRecombinant Fusion ProteinsSerineSubstrate SpecificityTransfectionConceptsProtein degradation assaysSubunit-specific inhibitorsProtein degradationDegradation assaysCellular proliferationChymotrypsin-like activityPeptidyl-glutamyl peptideEpoxyketone inhibitorsActive siteSuch interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancy
2000
Small-molecule inhibitors of the cell cycle
Crews C, Mohan R. Small-molecule inhibitors of the cell cycle. Current Opinion In Chemical Biology 2000, 4: 47-53. PMID: 10679374, DOI: 10.1016/s1367-5931(99)00050-2.Peer-Reviewed Original ResearchConceptsSmall molecule inhibitorsCell cycleNovel cell cycle inhibitorsCyclin-dependent kinasesCell cycle progressionCell cycle inhibitorsCytoskeletal dynamicsAnti-mitotic agentsNovel chemotherapeuticsAttractive targetInhibitorsScreening technologiesRecent advancesKinaseGreater specificityCycleChemotherapeutics