Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future
The PROteolysis TArgeting Chimeras (PROTACs) is an innovative technique for the selective degradation of target proteins via the ubiquitin–proteasome system. Compared with traditional protein inhibitor drugs, PROTACs exhibit advantages in the efficacy and selectivity of and in overcoming drug resist...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/24/8828 |
| _version_ | 1797456066219343872 |
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| author | Rui Li Miao Liu Zhenya Yang Jiao Li Yuxin Gao Ruirong Tan |
| author_facet | Rui Li Miao Liu Zhenya Yang Jiao Li Yuxin Gao Ruirong Tan |
| author_sort | Rui Li |
| collection | DOAJ |
| description | The PROteolysis TArgeting Chimeras (PROTACs) is an innovative technique for the selective degradation of target proteins via the ubiquitin–proteasome system. Compared with traditional protein inhibitor drugs, PROTACs exhibit advantages in the efficacy and selectivity of and in overcoming drug resistance in cancer therapy, providing new insights into the discovery of anti-cancer drugs. In the last two decades, many PROTAC molecules have been developed to induce the degradation of cancer-related targets, and they have been subjected to clinical trials. Here, we comprehensively review the historical milestones and latest updates in PROTAC technology. We focus on the structures and mechanisms of PROTACs and their application in targeting tumor-related targets. We have listed several representative PROTACs based on CRBN, VHL, MDM2, or cIAP1 E3 ligases, and PROTACs that are undergoing anti-cancer clinical trials. In addition, the limitations of the current research, as well as the future research directions are described to improve the PROTAC design and development for cancer therapy. |
| first_indexed | 2024-03-09T16:02:06Z |
| format | Article |
| id | doaj.art-3b98beabf45548d69ca7493e3f345628 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:02:06Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3b98beabf45548d69ca7493e3f3456282023-11-24T16:58:07ZengMDPI AGMolecules1420-30492022-12-012724882810.3390/molecules27248828Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and FutureRui Li0Miao Liu1Zhenya Yang2Jiao Li3Yuxin Gao4Ruirong Tan5Sichuan Cancer Hospital and Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, ChinaDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USAXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410083, ChinaTranslational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Institute for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, ChinaSichuan Cancer Hospital and Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, ChinaTranslational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Institute for Translational Chinese Medicine, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, ChinaThe PROteolysis TArgeting Chimeras (PROTACs) is an innovative technique for the selective degradation of target proteins via the ubiquitin–proteasome system. Compared with traditional protein inhibitor drugs, PROTACs exhibit advantages in the efficacy and selectivity of and in overcoming drug resistance in cancer therapy, providing new insights into the discovery of anti-cancer drugs. In the last two decades, many PROTAC molecules have been developed to induce the degradation of cancer-related targets, and they have been subjected to clinical trials. Here, we comprehensively review the historical milestones and latest updates in PROTAC technology. We focus on the structures and mechanisms of PROTACs and their application in targeting tumor-related targets. We have listed several representative PROTACs based on CRBN, VHL, MDM2, or cIAP1 E3 ligases, and PROTACs that are undergoing anti-cancer clinical trials. In addition, the limitations of the current research, as well as the future research directions are described to improve the PROTAC design and development for cancer therapy.https://www.mdpi.com/1420-3049/27/24/8828PROTACscancer therapytargeted protein degradationprotein degradation |
| spellingShingle | Rui Li Miao Liu Zhenya Yang Jiao Li Yuxin Gao Ruirong Tan Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future Molecules PROTACs cancer therapy targeted protein degradation protein degradation |
| title | Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future |
| title_full | Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future |
| title_fullStr | Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future |
| title_full_unstemmed | Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future |
| title_short | Proteolysis-Targeting Chimeras (PROTACs) in Cancer Therapy: Present and Future |
| title_sort | proteolysis targeting chimeras protacs in cancer therapy present and future |
| topic | PROTACs cancer therapy targeted protein degradation protein degradation |
| url | https://www.mdpi.com/1420-3049/27/24/8828 |
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