Featured Publications
Modular PROTAC Design for the Degradation of Oncogenic BCR‐ABL
Lai AC, Toure M, Hellerschmied D, Salami J, Jaime‐Figueroa S, Ko E, Hines J, Crews CM. Modular PROTAC Design for the Degradation of Oncogenic BCR‐ABL. Angewandte Chemie International Edition 2015, 55: 807-810. PMID: 26593377, PMCID: PMC4733637, DOI: 10.1002/anie.201507634.Peer-Reviewed Original Research
2024
Development of Ligands and Degraders Targeting MAGE-A3
Li K, Krone M, Butrin A, Bond M, Linhares B, Crews C. Development of Ligands and Degraders Targeting MAGE-A3. Journal Of The American Chemical Society 2024, 146: 24884-24891. PMID: 39190582, DOI: 10.1021/jacs.4c05393.Peer-Reviewed Original ResearchDNA-encoded librariesSmall molecule ligandsDevelopment of ligandsE3 ligase complexCocrystal structureChemical matterLigandPROTAC moleculesSmall moleculesLigase complexTargeted protein degradationMAGE-A3Substrate recognition moduleType I MAGEsRING E3 ligasesMoleculesCancer-selective expressionDimer interfaceImprove immunotherapy outcomesIncreased antigen presentationHigh tumor gradeE3 ligaseComplexBiochemical functionsCancer cell surfaceRegulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies
Raina K, Forbes C, Stronk R, Rappi J, Eastman K, Zaware N, Yu X, Li H, Bhardwaj A, Gerritz S, Forgione M, Hundt A, King M, Posner Z, Correia A, McGovern A, Puleo D, Chenard R, Mousseau J, Vergara J, Garvin E, Macaluso J, Martin M, Bassoli K, Jones K, Garcia M, Howard K, Yaggi M, Smith L, Chen J, Mayfield A, De Leon C, Hines J, Kayser-Bricker K, Crews C. Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies. Cell Chemical Biology 2024, 31: 1490-1502.e42. PMID: 39116881, PMCID: PMC11371387, DOI: 10.1016/j.chembiol.2024.07.005.Peer-Reviewed Original ResearchProtein-protein interactionsTarget proteinsTernary complexChemical biology studiesExpressed intracellular proteinStable ternary complexAnti-proliferative responseEssential proteinsProtein proximityEffector ligandsIntracellular proteinsCDK inhibitorsTarget-expressing cellsHeterobifunctional small moleculesSmall moleculesCell survivalTumor cellsTherapeutic modalitiesProteinSelective therapySmall molecule strategiesLigandBiological studiesDevelopment of a Small Molecule Downmodulator for the Transcription Factor Brachyury
Chase D, Bebenek A, Nie P, Jaime‐Figueroa S, Butrin A, Castro D, Hines J, Linhares B, Crews C. Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury. Angewandte Chemie International Edition 2024, 63: e202316496. PMID: 38348945, DOI: 10.1002/anie.202316496.Peer-Reviewed Original ResearchStructure-based drug design approachX-ray crystallographyDrug design approachMass spectrometryFDA-approved kinase inhibitorsX-raySmall moleculesChordoma cellsCrystallographyTumor cell growthCompoundsChordoma cell linesMoleculesChordoma growthOncogenic transcription factorKinase inhibitorsTranscription factorsDevelopment of a Small Molecule Downmodulator for the Transcription Factor Brachyury
Chase D, Bebenek A, Nie P, Jaime‐Figueroa S, Butrin A, Castro D, Hines J, Linhares B, Crews C. Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury. Angewandte Chemie 2024, 136 DOI: 10.1002/ange.202316496.Peer-Reviewed Original Research
2022
OligoTRAFTACs: A generalizable method for transcription factor degradation
Samarasinghe KTG, An E, Genuth MA, Chu L, Holley SA, Crews CM. OligoTRAFTACs: A generalizable method for transcription factor degradation. RSC Chemical Biology 2022, 3: 1144-1153. PMID: 36128504, PMCID: PMC9428672, DOI: 10.1039/d2cb00138a.Peer-Reviewed Original ResearchTranscription factorsOncogenic transcription factorGene expression circuitryTranscription factor degradationDNA binding abilityChordoma cell linesProteasomal degradationProteasomal pathwayZebrafish experimentsC-MycGeneralizable platformKey playersCell linesBrachyurySmall moleculesFactor degradationBinding abilityGeneralizable methodDegradationChimerasPathwayOligonucleotidePocketFirst generation
2020
Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs
Bond MJ, Chu L, Nalawansha DA, Li K, Crews CM. Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs. ACS Central Science 2020, 6: 1367-1375. PMID: 32875077, PMCID: PMC7453568, DOI: 10.1021/acscentsci.0c00411.Peer-Reviewed Original Research
2015
Small molecule‐induced catalytic ubiquitination of non‐natural substrates
Bondeson D, Pancevac C, Kruidenier L, Carter P, Churcher I, Crews C. Small molecule‐induced catalytic ubiquitination of non‐natural substrates. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.573.43.Peer-Reviewed Original Research
2014
Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System
Buckley DL, Crews CM. Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System. Angewandte Chemie International Edition 2014, 53: 2312-2330. PMID: 24459094, PMCID: PMC4348030, DOI: 10.1002/anie.201307761.Peer-Reviewed Original ResearchConceptsSmall molecule modulatorsProtein levelsSmall-molecule probesUbiquitin-proteasome systemActivity of proteinsIntracellular protein levelsBiological probesProteasome systemProtein degradationUbiquitin-proteasomeProtein activitySmall moleculesMolecule controlDruggable targetsProteomeProteasomeTargeted fashionProteinRemaining majorityGlobal increaseProbeUPSMoleculesDegradationMultiple strategies
2012
Exploring Biology with Small Organic Molecules
Aberle N, Crews C. Exploring Biology with Small Organic Molecules. 2012, 10-25. DOI: 10.1017/cbo9781139021500.004.Peer-Reviewed Original ResearchChemical geneticsSmall moleculesSmall organic moleculesFundamental biological processesProtein of interestGood target specificityOrganic moleculesSemisynthetic moleculesChemical genomicsBiological processesTarget specificityMoleculesGeneticsBiologyVast arrayActive ingredientsChemistryGenomicsCertain basic elementsHuman medicineTherapeuticsCompoundsPlantsProteinPhenotype
2010
Targeting the Undruggable Proteome: The Small Molecules of My Dreams
Crews CM. Targeting the Undruggable Proteome: The Small Molecules of My Dreams. Cell Chemical Biology 2010, 17: 551-555. PMID: 20609404, PMCID: PMC2925121, DOI: 10.1016/j.chembiol.2010.05.011.Peer-Reviewed Original ResearchConceptsTraditional genetic screensGenetic screenSmall moleculesUndruggable proteomeChemical genetic approachActive small moleculesSmall druglike moleculesSmall molecule librariesAreas of biologyChemical geneticsOrganismal levelDruglike moleculesDrug development effortsGenetic approachesCell biologyPharmaceutical interestBiological processesMolecule librariesPhenotypic changesMoleculesProteomeEarlier compoundsBiologyScreenNew bioassay
2006
Probing Protein Function with Small Molecules
Gough JD, Crews CM. Probing Protein Function with Small Molecules. Ernst Schering Foundation Symposium Proceedings 2006, 58: 61-74. PMID: 16708999, DOI: 10.1007/978-3-540-37635-4_5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiotinylationCombinatorial Chemistry TechniquesDrug DesignDrug Evaluation, PreclinicalGenomicsGreen Fluorescent ProteinsHumansKetonesModels, ChemicalMolecular Probe TechniquesNanotechnologyOligopeptidesPhosphorylationProtein BindingProteinsReceptors, AndrogenRecombinant Fusion ProteinsSerineSesquiterpenesSignal TransductionUbiquitin-Protein Ligases
1999
Chemical genetics: exploring and controlling cellular processes with chemical probes
Crews C, Splittgerber U. Chemical genetics: exploring and controlling cellular processes with chemical probes. Trends In Biochemical Sciences 1999, 24: 317-320. PMID: 10431176, DOI: 10.1016/s0968-0004(99)01425-5.Peer-Reviewed Original Research