Featured Publications
The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study
Burslem GM, Smith BE, Lai AC, Jaime-Figueroa S, McQuaid DC, Bondeson DP, Toure M, Dong H, Qian Y, Wang J, Crew AP, Hines J, Crews CM. The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study. Cell Chemical Biology 2017, 25: 67-77.e3. PMID: 29129716, PMCID: PMC5831399, DOI: 10.1016/j.chembiol.2017.09.009.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesProtein familyProtein degradationTyrosine kinaseDownstream signaling responseTargeted Protein DegradationDevelopment of PROTACsTargeted degradationEndogenous proteinsSignaling responseChimera technologyCell proliferationPROTACsPROTAC technologyKinaseKinase inhibitorsLigand showAdvantages of degradationReceptor tyrosine kinase inhibitorsTyrosine kinase inhibitorsInhibitionDegradationFamilyPowerful toolProteolysisChemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation
Schneekloth JS, Fonseca FN, Koldobskiy M, Mandal A, Deshaies R, Sakamoto K, Crews CM. Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation. Journal Of The American Chemical Society 2004, 126: 3748-3754. PMID: 15038727, DOI: 10.1021/ja039025z.Peer-Reviewed Original ResearchConceptsGreen fluorescent proteinProtein functionCell biological questionsGenetic model systemUbiquitin-proteasome pathwayChemical knockoutTargeted degradationBiological questionsProtein degradationGenetic strategiesGenetic controlGenetic lossTarget proteinsFluorescent proteinChimeric moleculesCultured cellsFKBP12 ligandsProteinProtein levelsModel systemWestern blotGeneral strategyFunction analysisVivo examplesFluorometric analysis
2022
Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation
Nalawansha DA, Li K, Hines J, Crews CM. Hijacking Methyl Reader Proteins for Nuclear-Specific Protein Degradation. Journal Of The American Chemical Society 2022, 144: 5594-5605. PMID: 35311258, PMCID: PMC10331457, DOI: 10.1021/jacs.2c00874.Peer-Reviewed Original ResearchConceptsE3 ligase complexLigase complexProtein degradationReader proteinsMethyl readersE3 ligaseProteasomal degradationPROTAC designProtein levelsProteinLigand pairsDrug discovery paradigmPROTACsNatural mechanismGeneralizable approachComplexesDiscovery paradigmCUL4BRD2DegradationLigaseL3MBTL3FKBP12Biological evaluationPromising strategy
2021
Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic
Hu Z, Crews CM. Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic. ChemBioChem 2021, 23: e202100270. PMID: 34494353, PMCID: PMC9395155, DOI: 10.1002/cbic.202100270.Peer-Reviewed Original ResearchElectrophilic Screening Platforms for Identifying Novel Covalent Ligands for E3 Ligases
Zheng S, Crews CM. Electrophilic Screening Platforms for Identifying Novel Covalent Ligands for E3 Ligases. Biochemistry 2021, 60: 2367-2370. PMID: 34152723, DOI: 10.1021/acs.biochem.1c00301.Peer-Reviewed Original Research
2015
HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins
Buckley DL, Raina K, Darricarrere N, Hines J, Gustafson JL, Smith IE, Miah AH, Harling JD, Crews CM. HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins. ACS Chemical Biology 2015, 10: 1831-1837. PMID: 26070106, PMCID: PMC4629848, DOI: 10.1021/acschembio.5b00442.Peer-Reviewed Original ResearchConceptsChemical probesMore drug-like propertiesFusion proteinSmall-molecule PROTACsProtein degradationDrug-like propertiesE3 ligase ligandChemical genetic toolsSpecific E3 ligasesProtein of interestVHL ligandsHaloTag fusion proteinsE3 ligasesGenetic toolsHeterobifunctional moleculesNumerous proteinsHaloPROTACLigandsPROTACsProteinNovel classAttractive strategyDegradationProbeLigases
1998
Eponemycin analogues: syntheses and use as probes of angiogenesis
Sin N, Meng L, Auth H, Crews C. Eponemycin analogues: syntheses and use as probes of angiogenesis. Bioorganic & Medicinal Chemistry 1998, 6: 1209-1217. PMID: 9784862, DOI: 10.1016/s0968-0896(98)00089-3.Peer-Reviewed Original Research