2023
Protein degraders enter the clinic — a new approach to cancer therapy
Chirnomas D, Hornberger K, Crews C. Protein degraders enter the clinic — a new approach to cancer therapy. Nature Reviews Clinical Oncology 2023, 20: 265-278. PMID: 36781982, DOI: 10.1038/s41571-023-00736-3.Peer-Reviewed Original ResearchConceptsPhase III trialsCancer therapyNovel therapeutic modalitiesIII trialsClinical trialsPreclinical modelsClinical studiesTherapeutic modalitiesPharmacokinetic dataSmall molecule inhibitorsDisease pathogenesisClinical testingTumor typesDrug concentrationsPreclinical researchCancer treatmentPhase IFirst safetyUbiquitin-proteasome systemPatientsProtein degradersTherapyMore evidenceTrialsRigorous evaluation
2022
PROTACs: past, present and future
Li K, Crews CM. PROTACs: past, present and future. Chemical Society Reviews 2022, 51: 5214-5236. PMID: 35671157, PMCID: PMC10237031, DOI: 10.1039/d2cs00193d.Peer-Reviewed Original ResearchConceptsProtein of interestProteolysis-targeting chimerasUbiquitin-proteasome systemE3 ubiquitin ligaseSmall molecule inhibitorsUbiquitin ligaseNonenzymatic functionProtein degradationHeterobifunctional moleculesDrug resistance mechanismsMolecule inhibitorsSubsequent degradationUbiquitinationLigasePromising therapeuticsProteinChimerasPotential toxicityDegradationMechanism
2021
Major 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
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