Degradation of proteins by PROTACs and other strategies
Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identifi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-02-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383519306914 |
| _version_ | 1811274231143464960 |
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| author | Yang Wang Xueyang Jiang Feng Feng Wenyuan Liu Haopeng Sun |
| author_facet | Yang Wang Xueyang Jiang Feng Feng Wenyuan Liu Haopeng Sun |
| author_sort | Yang Wang |
| collection | DOAJ |
| description | Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identification of the structure of the first ternary eutectic complex, extra-terminal domain-4-PROTAC-Von-Hippel-Lindau (BRD4-PROTAC-VHL), and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019. These discoveries strongly proved the value of the PROTAC strategy. In this perspective, we summarized recent meaningful research of PROTAC, including the types of degradation proteins, preliminary biological data in vitro and in vivo, and new E3 ubiquitin ligases. Importantly, the molecular design, optimization strategy and clinical application of candidate molecules are highlighted in detail. Future perspectives for development of advanced PROTAC in medical fields have also been discussed systematically. KEY WORDS: Protein degradation, PROTAC, Ubiquitin−proteasome system, E3 ubiquitin ligase, Target protein, Heterobifunctional molecule |
| first_indexed | 2024-04-12T23:15:18Z |
| format | Article |
| id | doaj.art-bcabdc2eb59e4a3faa27a5bb8131d408 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-04-12T23:15:18Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-bcabdc2eb59e4a3faa27a5bb8131d4082022-12-22T03:12:41ZengElsevierActa Pharmaceutica Sinica B2211-38352020-02-01102207238Degradation of proteins by PROTACs and other strategiesYang Wang0Xueyang Jiang1Feng Feng2Wenyuan Liu3Haopeng Sun4Department of Pharmaceutical Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, ChinaDepartment of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, ChinaJiangsu Food and Pharmaceutical Science College, Huaian 223003, China; Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, ChinaDepartment of Pharmaceutical Analysis, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China; Corresponding authors.Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China; Corresponding authors.Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identification of the structure of the first ternary eutectic complex, extra-terminal domain-4-PROTAC-Von-Hippel-Lindau (BRD4-PROTAC-VHL), and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019. These discoveries strongly proved the value of the PROTAC strategy. In this perspective, we summarized recent meaningful research of PROTAC, including the types of degradation proteins, preliminary biological data in vitro and in vivo, and new E3 ubiquitin ligases. Importantly, the molecular design, optimization strategy and clinical application of candidate molecules are highlighted in detail. Future perspectives for development of advanced PROTAC in medical fields have also been discussed systematically. KEY WORDS: Protein degradation, PROTAC, Ubiquitin−proteasome system, E3 ubiquitin ligase, Target protein, Heterobifunctional moleculehttp://www.sciencedirect.com/science/article/pii/S2211383519306914 |
| spellingShingle | Yang Wang Xueyang Jiang Feng Feng Wenyuan Liu Haopeng Sun Degradation of proteins by PROTACs and other strategies Acta Pharmaceutica Sinica B |
| title | Degradation of proteins by PROTACs and other strategies |
| title_full | Degradation of proteins by PROTACs and other strategies |
| title_fullStr | Degradation of proteins by PROTACs and other strategies |
| title_full_unstemmed | Degradation of proteins by PROTACs and other strategies |
| title_short | Degradation of proteins by PROTACs and other strategies |
| title_sort | degradation of proteins by protacs and other strategies |
| url | http://www.sciencedirect.com/science/article/pii/S2211383519306914 |
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