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Recent Advances in PROTACs for Drug Targeted Protein Research
Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499226/ https://www.ncbi.nlm.nih.gov/pubmed/36142231 http://dx.doi.org/10.3390/ijms231810328 |
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author | Yao, Tingting Xiao, Heng Wang, Hong Xu, Xiaowei |
author_facet | Yao, Tingting Xiao, Heng Wang, Hong Xu, Xiaowei |
author_sort | Yao, Tingting |
collection | PubMed |
description | Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin–proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC. |
format | Online Article Text |
id | pubmed-9499226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94992262022-09-23 Recent Advances in PROTACs for Drug Targeted Protein Research Yao, Tingting Xiao, Heng Wang, Hong Xu, Xiaowei Int J Mol Sci Review Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin–proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC. MDPI 2022-09-07 /pmc/articles/PMC9499226/ /pubmed/36142231 http://dx.doi.org/10.3390/ijms231810328 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Yao, Tingting Xiao, Heng Wang, Hong Xu, Xiaowei Recent Advances in PROTACs for Drug Targeted Protein Research |
title | Recent Advances in PROTACs for Drug Targeted Protein Research |
title_full | Recent Advances in PROTACs for Drug Targeted Protein Research |
title_fullStr | Recent Advances in PROTACs for Drug Targeted Protein Research |
title_full_unstemmed | Recent Advances in PROTACs for Drug Targeted Protein Research |
title_short | Recent Advances in PROTACs for Drug Targeted Protein Research |
title_sort | recent advances in protacs for drug targeted protein research |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499226/ https://www.ncbi.nlm.nih.gov/pubmed/36142231 http://dx.doi.org/10.3390/ijms231810328 |
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