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Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment

Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interact...

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Detalles Bibliográficos
Autores principales: Wu, Hongyu, Yao, Hong, He, Chen, Jia, Yilin, Zhu, Zheying, Xu, Shengtao, Li, Dahong, Xu, Jinyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513498/
https://www.ncbi.nlm.nih.gov/pubmed/36176907
http://dx.doi.org/10.1016/j.apsb.2022.03.019
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author Wu, Hongyu
Yao, Hong
He, Chen
Jia, Yilin
Zhu, Zheying
Xu, Shengtao
Li, Dahong
Xu, Jinyi
author_facet Wu, Hongyu
Yao, Hong
He, Chen
Jia, Yilin
Zhu, Zheying
Xu, Shengtao
Li, Dahong
Xu, Jinyi
author_sort Wu, Hongyu
collection PubMed
description Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification.
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spelling pubmed-95134982022-09-28 Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment Wu, Hongyu Yao, Hong He, Chen Jia, Yilin Zhu, Zheying Xu, Shengtao Li, Dahong Xu, Jinyi Acta Pharm Sin B Review Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification. Elsevier 2022-09 2022-03-31 /pmc/articles/PMC9513498/ /pubmed/36176907 http://dx.doi.org/10.1016/j.apsb.2022.03.019 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Wu, Hongyu
Yao, Hong
He, Chen
Jia, Yilin
Zhu, Zheying
Xu, Shengtao
Li, Dahong
Xu, Jinyi
Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title_full Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title_fullStr Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title_full_unstemmed Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title_short Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment
title_sort molecular glues modulate protein functions by inducing protein aggregation: a promising therapeutic strategy of small molecules for disease treatment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513498/
https://www.ncbi.nlm.nih.gov/pubmed/36176907
http://dx.doi.org/10.1016/j.apsb.2022.03.019
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