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Title:
Protein degradation technology: a strategic paradigm shift in drug discovery | Journal of Hematology & Oncology
Description:
Targeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
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- Endocytosis and autophagy: exploitation or cooperation?
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headline:Protein degradation technology: a strategic paradigm shift in drug discovery
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datePublished:2021-09-06T00:00:00Z
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Protein degradation
Degradation pathway
Degradation technology
PROTAC
Monomeric degraders
Oncology
Hematology
Cancer Research
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headline:Protein degradation technology: a strategic paradigm shift in drug discovery
description:Targeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
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Protein degradation
Degradation pathway
Degradation technology
PROTAC
Monomeric degraders
Oncology
Hematology
Cancer Research
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email:[email protected]
name:Jiang-Jiang Qin
url:http://orcid.org/0000-0002-8559-616X
affiliation:
name:The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
address:
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
type:PostalAddress
type:Organization
name:Chinese Academy of Sciences
address:
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
type:PostalAddress
type:Organization
name:Zhejiang Chinese Medical University
address:
name:School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China
name:Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China
name:School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
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