2021
Targeted protein degradation: A promise for undruggable proteins
Samarasinghe KTG, Crews CM. Targeted protein degradation: A promise for undruggable proteins. Cell Chemical Biology 2021, 28: 934-951. PMID: 34004187, PMCID: PMC8286327, DOI: 10.1016/j.chembiol.2021.04.011.Peer-Reviewed Original ResearchConceptsProteolysis Targeting ChimerasUndruggable proteinsDisease-causing proteinsProtein degradation strategiesProteostasis mechanismsProtein homeostasisTranscription factorsProtein degradationHeterobifunctional moleculesProteinDegradation strategiesDisease initiationBiological effectsProteostasisDegradationPotential therapeutic modalityHomeostasisChimerasCellsAccumulation
2016
BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825, Causes Sustained Degradation of BRD4 and Modulation of Chemokine Receptors, Cell Adhesion and Metabolic Targets in Leukemia Resulting in Profound Anti-Leukemic Effects
Piya S, Bhattacharya S, Mu H, Lorenzi P, McQueen T, Davis E, Ruvolo V, Baran N, Qian Y, Crews C, Kantarjian H, Andreeff M, Borthakur G. BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825, Causes Sustained Degradation of BRD4 and Modulation of Chemokine Receptors, Cell Adhesion and Metabolic Targets in Leukemia Resulting in Profound Anti-Leukemic Effects. Blood 2016, 128: 748. DOI: 10.1182/blood.v128.22.748.748.Peer-Reviewed Original ResearchProteolysis Targeting ChimerasARV-825Cell adhesionExtra-terminal domain (BET) familyOverexpression of PIM1Amino acid transportersDegradation of BRD4Production of ATPGene expression profilingMesenchymal stromal cellsCell linesImportant amino acidsTranscription of oncogenesBcl-2 family moleculesStroma-mediated drug resistanceWnt/β-catenin pathwayNutrient acquisitionRegulatory machineryFlow cytometryEnhancer complexTranscriptional coactivatorSmall-molecule BRD4 inhibitorsDomain familyEpigenetic eventsProteomic analysis