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