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 knockoutCellsMutant-selective degradation by BRAF-targeting PROTACs
Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, Crews CM. Mutant-selective degradation by BRAF-targeting PROTACs. Nature Communications 2021, 12: 920. PMID: 33568647, PMCID: PMC7876048, DOI: 10.1038/s41467-021-21159-7.Peer-Reviewed Original ResearchConceptsInhibitor-based therapyBRAF inhibitor-based therapiesBRAF missense mutationsCancer cell growthBRAF V600Current treatmentNew therapiesTherapeutic windowXenograft modelBRAF mutantMutant BRAFVivo efficacyDrug modalitiesRaf family membersProteolysis targeting chimera (PROTAC) technologyTherapyBRAFMissense mutationsFamily membersBRAFWTCell growthDegree of selectivityInactivated conformationPatientsV600
2015
Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging
Gustafson JL, Neklesa TK, Cox CS, Roth AG, Buckley DL, Tae HS, Sundberg TB, Stagg DB, Hines J, McDonnell DP, Norris JD, Crews CM. Small‐Molecule‐Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging. Angewandte Chemie International Edition 2015, 54: 9659-9662. PMID: 26083457, PMCID: PMC4547777, DOI: 10.1002/anie.201503720.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen Receptor AntagonistsAntineoplastic AgentsBenzamidesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmHumansHydrophobic and Hydrophilic InteractionsMaleNitrilesPhenylthiohydantoinPoint MutationProstateProstatic NeoplasmsProteolysisReceptors, AndrogenSmall Molecule LibrariesConceptsSelective androgen receptor degradersAndrogen receptorAR mutationsAndrogen-dependent prostate cancer cell lineSecond-generation AR antagonistsAR degradationProstate tumor cell proliferationProstate cancer cell linesAR target genesTumor cell proliferationAntitumor chemotherapeutic agentsCancer cell linesAR antagonistsChemotherapeutic agentsCell proliferationAR ligandsCell linesAntagonistTumor strategyResistance mechanismsReceptorsRecent studiesProliferationTarget genesDependent transcriptionHijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4
Lu J, Qian Y, Altieri M, Dong H, Wang J, Raina K, Hines J, Winkler JD, Crew AP, Coleman K, Crews CM. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Cell Chemical Biology 2015, 22: 755-763. PMID: 26051217, PMCID: PMC4475452, DOI: 10.1016/j.chembiol.2015.05.009.Peer-Reviewed Original ResearchAcetanilidesAdaptor Proteins, Signal TransducingApoptosisAzepinesCell Cycle ProteinsCell Line, TumorCell ProliferationHeterocyclic Compounds, 3-RingHumansNuclear ProteinsPeptide HydrolasesProto-Oncogene Proteins c-mycSignal TransductionThalidomideTranscription FactorsTriazolesUbiquitin-Protein Ligases
2008
Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer
Rodriguez-Gonzalez A, Cyrus K, Salcius M, Kim K, Crews CM, Deshaies RJ, Sakamoto KM. Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene 2008, 27: 7201-7211. PMID: 18794799, PMCID: PMC5573236, DOI: 10.1038/onc.2008.320.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBlotting, WesternBreast NeoplasmsCell CycleCell Line, TumorCell ProliferationDihydrotestosteroneDrug Delivery SystemsEstradiolEstrogen Receptor alphaFemaleFlow CytometryHumansHypoxia-Inducible Factor 1, alpha SubunitMaleNeoplasms, Hormone-DependentProstatic NeoplasmsProteasome Endopeptidase ComplexReceptors, AndrogenReceptors, SteroidRecombinant Fusion ProteinsUbiquitinationConceptsBreast cancer cellsProstate cancer cellsCancer cellsAndrogen-dependent prostate cancer cellsHormone-dependent cell linesEstrogen-independent breast cancer cellsEstrogen-dependent breast cancer cellsHormone receptorsHormone-dependent breastG1 arrestDegradation of ERαSteroid hormone receptorsERα expressionProgesterone receptorAndrogen receptorProstate cancerEstrogen receptorCyclin D1Retinoblastoma phosphorylationReceptorsCell linesERαBreastProliferationProteasome-dependent manner