Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs
There are several challenges towards the development and clinical use of small molecule inhibitors, which are currently the main type of targeted therapies towards intracellular proteins. PROteolysis-TArgeting Chimeras (PROTACs) exploit the intracellular ubiquitin-proteasome system to selectively de...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-10-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396418303621 |
| _version_ | 1818274992883761152 |
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| author | Sainan An Liwu Fu |
| author_facet | Sainan An Liwu Fu |
| author_sort | Sainan An |
| collection | DOAJ |
| description | There are several challenges towards the development and clinical use of small molecule inhibitors, which are currently the main type of targeted therapies towards intracellular proteins. PROteolysis-TArgeting Chimeras (PROTACs) exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins. Recently, small-molecule PROTACs with high potency have been frequently reported. In this review, we summarize the emerging characteristics of small-molecule PROTACs, such as inducing a rapid, profound and sustained degradation, inducing a robust inhibition of downstream signals, displaying enhanced target selectivity, and overcoming resistance to small molecule inhibitors. In tumor xenografts, small-molecule PROTACs can significantly attenuate tumor progression. In addition, we also introduce recent developments of the PROTAC technology such as homo-PROTACs. The outstanding advantages over traditional small-molecule drugs and the promising preclinical data suggest that small-molecule PROTAC technology has the potential to greatly promote the development of targeted therapy drugs. Keywords: PROTAC, Induced protein degradation, E3 ligases, Ubiquitin-proteasome system, Targeted therapy drugs |
| first_indexed | 2024-12-12T22:22:40Z |
| format | Article |
| id | doaj.art-27843e16c0154ac3a6bdcd96c81e2f87 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-12T22:22:40Z |
| publishDate | 2018-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-27843e16c0154ac3a6bdcd96c81e2f872022-12-22T00:09:51ZengElsevierEBioMedicine2352-39642018-10-0136553562Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugsSainan An0Liwu Fu1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR ChinaCorresponding author.; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR ChinaThere are several challenges towards the development and clinical use of small molecule inhibitors, which are currently the main type of targeted therapies towards intracellular proteins. PROteolysis-TArgeting Chimeras (PROTACs) exploit the intracellular ubiquitin-proteasome system to selectively degrade target proteins. Recently, small-molecule PROTACs with high potency have been frequently reported. In this review, we summarize the emerging characteristics of small-molecule PROTACs, such as inducing a rapid, profound and sustained degradation, inducing a robust inhibition of downstream signals, displaying enhanced target selectivity, and overcoming resistance to small molecule inhibitors. In tumor xenografts, small-molecule PROTACs can significantly attenuate tumor progression. In addition, we also introduce recent developments of the PROTAC technology such as homo-PROTACs. The outstanding advantages over traditional small-molecule drugs and the promising preclinical data suggest that small-molecule PROTAC technology has the potential to greatly promote the development of targeted therapy drugs. Keywords: PROTAC, Induced protein degradation, E3 ligases, Ubiquitin-proteasome system, Targeted therapy drugshttp://www.sciencedirect.com/science/article/pii/S2352396418303621 |
| spellingShingle | Sainan An Liwu Fu Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs EBioMedicine |
| title | Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs |
| title_full | Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs |
| title_fullStr | Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs |
| title_full_unstemmed | Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs |
| title_short | Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs |
| title_sort | small molecule protacs an emerging and promising approach for the development of targeted therapy drugs |
| url | http://www.sciencedirect.com/science/article/pii/S2352396418303621 |
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