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Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)

Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC...

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Autores principales: Luo, Yuxiang, Li, Huilin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700698/
https://www.ncbi.nlm.nih.gov/pubmed/33266366
http://dx.doi.org/10.3390/ijms21228828
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author Luo, Yuxiang
Li, Huilin
author_facet Luo, Yuxiang
Li, Huilin
author_sort Luo, Yuxiang
collection PubMed
description Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC isoform selectivity, exhibiting undesirable side effects. A major issue with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Except for HDAC8, Class I HDACs (1, 2 and 3) are recruited to large multiprotein complexes to function. Therefore, there are rising needs to develop new, hopefully, therapeutically efficacious HDAC inhibitors with isoform or complex selectivity. Here, upon the introduction of the structures of Class I HDACs and their complexes, we provide an up-to-date overview of the structure-based discovery of Class I HDAC inhibitors, including pan-, isoform-selective and complex-specific inhibitors, aiming to provide an insight into the discovery of additional HDAC inhibitors with greater selectivity, specificity and therapeutic utility.
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spelling pubmed-77006982020-11-30 Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs) Luo, Yuxiang Li, Huilin Int J Mol Sci Review Class I histone deacetylases (HDACs) are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections and neurological diseases. Although six HDAC inhibitors are now licensed for clinical treatments, they are all pan-inhibitors with little or no HDAC isoform selectivity, exhibiting undesirable side effects. A major issue with the currently available HDAC inhibitors is that they have limited specificity and target multiple deacetylases. Except for HDAC8, Class I HDACs (1, 2 and 3) are recruited to large multiprotein complexes to function. Therefore, there are rising needs to develop new, hopefully, therapeutically efficacious HDAC inhibitors with isoform or complex selectivity. Here, upon the introduction of the structures of Class I HDACs and their complexes, we provide an up-to-date overview of the structure-based discovery of Class I HDAC inhibitors, including pan-, isoform-selective and complex-specific inhibitors, aiming to provide an insight into the discovery of additional HDAC inhibitors with greater selectivity, specificity and therapeutic utility. MDPI 2020-11-22 /pmc/articles/PMC7700698/ /pubmed/33266366 http://dx.doi.org/10.3390/ijms21228828 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Luo, Yuxiang
Li, Huilin
Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title_full Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title_fullStr Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title_full_unstemmed Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title_short Structure-Based Inhibitor Discovery of Class I Histone Deacetylases (HDACs)
title_sort structure-based inhibitor discovery of class i histone deacetylases (hdacs)
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700698/
https://www.ncbi.nlm.nih.gov/pubmed/33266366
http://dx.doi.org/10.3390/ijms21228828
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