Discovery of E3 Ligase Ligands for Target Protein Degradation
Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/19/6515 |
| _version_ | 1797477938884509696 |
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| author | Jaeseok Lee Youngjun Lee Young Mee Jung Ju Hyun Park Hyuk Sang Yoo Jongmin Park |
| author_facet | Jaeseok Lee Youngjun Lee Young Mee Jung Ju Hyun Park Hyuk Sang Yoo Jongmin Park |
| author_sort | Jaeseok Lee |
| collection | DOAJ |
| description | Target protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligands have been mostly limited to either CRBN or VHL ligands. Those PROTACs showed their limitation due to the cell type specific expression of E3 ligases and recently reported resistance toward PROTACs with CRBN ligands or VHL ligands. To overcome these hurdles, the discovery of various E3 ligase ligands has been spotlighted to improve the current PROTAC technology. This review focuses on currently reported E3 ligase ligands and their application in the development of PROTACs. |
| first_indexed | 2024-03-09T21:24:52Z |
| format | Article |
| id | doaj.art-a2b8074252ea4491918eedb8497ccec6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:24:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a2b8074252ea4491918eedb8497ccec62023-11-23T21:12:41ZengMDPI AGMolecules1420-30492022-10-012719651510.3390/molecules27196515Discovery of E3 Ligase Ligands for Target Protein DegradationJaeseok Lee0Youngjun Lee1Young Mee Jung2Ju Hyun Park3Hyuk Sang Yoo4Jongmin Park5Department of Chemistry, Kangwon National University, Chuncheon 24341, KoreaDepartment of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USADepartment of Chemistry, Kangwon National University, Chuncheon 24341, KoreaKangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon 24341, KoreaKangwon Radiation Convergence Research Support Center, Kangwon National University, Chuncheon 24341, KoreaDepartment of Chemistry, Kangwon National University, Chuncheon 24341, KoreaTarget protein degradation has emerged as a promising strategy for the discovery of novel therapeutics during the last decade. Proteolysis-targeting chimera (PROTAC) harnesses a cellular ubiquitin-dependent proteolysis system for the efficient degradation of a protein of interest. PROTAC consists of a target protein ligand and an E3 ligase ligand so that it enables the target protein degradation owing to the induced proximity with ubiquitin ligases. Although a great number of PROTACs has been developed so far using previously reported ligands of proteins for their degradation, E3 ligase ligands have been mostly limited to either CRBN or VHL ligands. Those PROTACs showed their limitation due to the cell type specific expression of E3 ligases and recently reported resistance toward PROTACs with CRBN ligands or VHL ligands. To overcome these hurdles, the discovery of various E3 ligase ligands has been spotlighted to improve the current PROTAC technology. This review focuses on currently reported E3 ligase ligands and their application in the development of PROTACs.https://www.mdpi.com/1420-3049/27/19/6515target protein degradationPROTACE3 ligase ligand |
| spellingShingle | Jaeseok Lee Youngjun Lee Young Mee Jung Ju Hyun Park Hyuk Sang Yoo Jongmin Park Discovery of E3 Ligase Ligands for Target Protein Degradation Molecules target protein degradation PROTAC E3 ligase ligand |
| title | Discovery of E3 Ligase Ligands for Target Protein Degradation |
| title_full | Discovery of E3 Ligase Ligands for Target Protein Degradation |
| title_fullStr | Discovery of E3 Ligase Ligands for Target Protein Degradation |
| title_full_unstemmed | Discovery of E3 Ligase Ligands for Target Protein Degradation |
| title_short | Discovery of E3 Ligase Ligands for Target Protein Degradation |
| title_sort | discovery of e3 ligase ligands for target protein degradation |
| topic | target protein degradation PROTAC E3 ligase ligand |
| url | https://www.mdpi.com/1420-3049/27/19/6515 |
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