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Medicinal chemistry advances in targeting class I histone deacetylases
Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Open Exploration Publishing
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497394/ https://www.ncbi.nlm.nih.gov/pubmed/37711592 http://dx.doi.org/10.37349/etat.2023.00166 |
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author | Abdallah, Diaaeldin I. de Araujo, Elvin D. Patel, Naman H. Hasan, Lina S. Moriggl, Richard Krämer, Oliver H. Gunning, Patrick T. |
author_facet | Abdallah, Diaaeldin I. de Araujo, Elvin D. Patel, Naman H. Hasan, Lina S. Moriggl, Richard Krämer, Oliver H. Gunning, Patrick T. |
author_sort | Abdallah, Diaaeldin I. |
collection | PubMed |
description | Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression—most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors. |
format | Online Article Text |
id | pubmed-10497394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Open Exploration Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-104973942023-09-14 Medicinal chemistry advances in targeting class I histone deacetylases Abdallah, Diaaeldin I. de Araujo, Elvin D. Patel, Naman H. Hasan, Lina S. Moriggl, Richard Krämer, Oliver H. Gunning, Patrick T. Explor Target Antitumor Ther Review Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression—most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors. Open Exploration Publishing 2023 2023-08-31 /pmc/articles/PMC10497394/ /pubmed/37711592 http://dx.doi.org/10.37349/etat.2023.00166 Text en © The Author(s) 2023. https://creativecommons.org/licenses/by/4.0/This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Abdallah, Diaaeldin I. de Araujo, Elvin D. Patel, Naman H. Hasan, Lina S. Moriggl, Richard Krämer, Oliver H. Gunning, Patrick T. Medicinal chemistry advances in targeting class I histone deacetylases |
title | Medicinal chemistry advances in targeting class I histone deacetylases |
title_full | Medicinal chemistry advances in targeting class I histone deacetylases |
title_fullStr | Medicinal chemistry advances in targeting class I histone deacetylases |
title_full_unstemmed | Medicinal chemistry advances in targeting class I histone deacetylases |
title_short | Medicinal chemistry advances in targeting class I histone deacetylases |
title_sort | medicinal chemistry advances in targeting class i histone deacetylases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497394/ https://www.ncbi.nlm.nih.gov/pubmed/37711592 http://dx.doi.org/10.37349/etat.2023.00166 |
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