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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...

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Detalles Bibliográficos
Autores principales: Yao, Tingting, Xiao, Heng, Wang, Hong, Xu, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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