2017
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells
Sun B, Fiskus W, Qian Y, Rajapakshe K, Raina K, Coleman KG, Crew AP, Shen A, Saenz DT, Mill CP, Nowak AJ, Jain N, Zhang L, Wang M, Khoury JD, Coarfa C, Crews CM, Bhalla KN. BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells. Leukemia 2017, 32: 343-352. PMID: 28663582, DOI: 10.1038/leu.2017.207.Peer-Reviewed Original ResearchConceptsMantle cell lymphoma cellsMCL cellsCell lymphoma cellsARV-825ARV-771Lymphoma cellsGreater survival improvementSuperior preclinical activityCDK4/6 inhibitor palbociclibNuclear factor-κB (NF-κB) target genesExtraterminal protein inhibitorSurvival improvementInhibitor palbociclibPreclinical activityCDKN1A/p21Inhibitor treatmentSuperior pharmacological propertiesVivo growthCyclin D1Pharmacological propertiesProtein expressionMore apoptosisVivo evaluationIncomplete inhibitionC-Myc
2016
Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells
Sun B, Fiskus W, Zhang L, Raina K, Coleman K, Winkler J, Qian Y, Crew A, Shen A, Saenz D, Mill C, Wang M, Crews C, Bhalla K. Novel BET Protein Proteolysis Targeting Chimeras (BETP-PROTACs) Exert Potent Single Agent and Synergistic Activity with Ibrutinib and Venetoclax Against Human Mantle Cell Lymphoma Cells. Blood 2016, 128: 1058. DOI: 10.1182/blood.v128.22.1058.1058.Peer-Reviewed Original ResearchTarget gene expressionBruton's tyrosine kinaseC-MycARV-825Transcription factorsPrimary MCL cellsTranscriptional activityGene expressionTyrosine kinaseBcl-xLE3 ubiquitin ligase activityMCL cellsUbiquitin ligase activityHuman mantle cell lymphoma cellsB-cell receptor signalingCell receptor signalingBinding of BRD4Regulation of mRNAInk4a/ArfAcetylated chromatinCopy number gainsLigase activityHematopoietic progenitor cellsBET proteinsBETi treatment