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PROTACs: A novel strategy for cancer drug discovery and development
Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase an...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227178/ https://www.ncbi.nlm.nih.gov/pubmed/37261210 http://dx.doi.org/10.1002/mco2.290 |
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author | Han, Xin Sun, Yi |
author_facet | Han, Xin Sun, Yi |
author_sort | Han, Xin |
collection | PubMed |
description | Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase and its small molecule recruiter), and a chemical linker that hooks first two components together. In the past 20 years, we have witnessed advancement of multiple PROTAC degraders into the clinical trials for anticancer therapies. However, one of the major challenges of PROTAC technology is that only very limited number of E3 ligase recruiters are currently available as E3 ligand for targeted protein degradation (TPD), although human genome encodes more than 600 E3 ligases. Thus, there is an urgent need to identify additional effective E3 ligase recruiters for TPD applications. In this review, we summarized the existing RING‐type E3 ubiquitin ligase and their small molecule recruiters that act as effective E3 ligands of PROTAC degraders and their application in anticancer drug discovery. We believe that this review could serve as a reference in future development of efficient E3 ligands of PROTAC technology for cancer drug discovery and development. |
format | Online Article Text |
id | pubmed-10227178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102271782023-05-31 PROTACs: A novel strategy for cancer drug discovery and development Han, Xin Sun, Yi MedComm (2020) Reviews Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase and its small molecule recruiter), and a chemical linker that hooks first two components together. In the past 20 years, we have witnessed advancement of multiple PROTAC degraders into the clinical trials for anticancer therapies. However, one of the major challenges of PROTAC technology is that only very limited number of E3 ligase recruiters are currently available as E3 ligand for targeted protein degradation (TPD), although human genome encodes more than 600 E3 ligases. Thus, there is an urgent need to identify additional effective E3 ligase recruiters for TPD applications. In this review, we summarized the existing RING‐type E3 ubiquitin ligase and their small molecule recruiters that act as effective E3 ligands of PROTAC degraders and their application in anticancer drug discovery. We believe that this review could serve as a reference in future development of efficient E3 ligands of PROTAC technology for cancer drug discovery and development. John Wiley and Sons Inc. 2023-05-29 /pmc/articles/PMC10227178/ /pubmed/37261210 http://dx.doi.org/10.1002/mco2.290 Text en © 2023 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Reviews Han, Xin Sun, Yi PROTACs: A novel strategy for cancer drug discovery and development |
title | PROTACs: A novel strategy for cancer drug discovery and development |
title_full | PROTACs: A novel strategy for cancer drug discovery and development |
title_fullStr | PROTACs: A novel strategy for cancer drug discovery and development |
title_full_unstemmed | PROTACs: A novel strategy for cancer drug discovery and development |
title_short | PROTACs: A novel strategy for cancer drug discovery and development |
title_sort | protacs: a novel strategy for cancer drug discovery and development |
topic | Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227178/ https://www.ncbi.nlm.nih.gov/pubmed/37261210 http://dx.doi.org/10.1002/mco2.290 |
work_keys_str_mv | AT hanxin protacsanovelstrategyforcancerdrugdiscoveryanddevelopment AT sunyi protacsanovelstrategyforcancerdrugdiscoveryanddevelopment |