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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...

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Autores principales: Abdallah, Diaaeldin I., de Araujo, Elvin D., Patel, Naman H., Hasan, Lina S., Moriggl, Richard, Krämer, Oliver H., Gunning, Patrick T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Open Exploration Publishing 2023
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.
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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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