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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Format: | Article |
Language: | English |
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Open Exploration Publishing Inc.
2023-08-01
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Series: | Exploration of Targeted Anti-tumor Therapy |
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Online Access: | https://www.explorationpub.com/Journals/etat/Article/1002166 |
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author | Diaaeldin I. Abdallah Elvin D. de Araujo Naman H. Patel Lina S. Hasan Richard Moriggl Oliver H. Krämer Patrick T. Gunning |
author_facet | Diaaeldin I. Abdallah Elvin D. de Araujo Naman H. Patel Lina S. Hasan Richard Moriggl Oliver H. Krämer Patrick T. Gunning |
author_sort | Diaaeldin I. Abdallah |
collection | DOAJ |
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. |
first_indexed | 2024-03-12T02:15:54Z |
format | Article |
id | doaj.art-34581887751b4ed39c2cde49dcc5b039 |
institution | Directory Open Access Journal |
issn | 2692-3114 |
language | English |
last_indexed | 2024-03-12T02:15:54Z |
publishDate | 2023-08-01 |
publisher | Open Exploration Publishing Inc. |
record_format | Article |
series | Exploration of Targeted Anti-tumor Therapy |
spelling | doaj.art-34581887751b4ed39c2cde49dcc5b0392023-09-06T08:14:41ZengOpen Exploration Publishing Inc.Exploration of Targeted Anti-tumor Therapy2692-31142023-08-014475777910.37349/etat.2023.00166Medicinal chemistry advances in targeting class I histone deacetylasesDiaaeldin I. Abdallah0Elvin D. de Araujo1https://orcid.org/0000-0003-0716-2830Naman H. Patel2Lina S. Hasan3Richard Moriggl4https://orcid.org/0000-0003-0918-9463Oliver H. Krämer5https://orcid.org/0000-0003-3973-045XPatrick T. Gunning6https://orcid.org/0000-0003-0654-735XDepartment of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada; Department of Chemistry, University of Toronto, Toronto, Ontario M5S 2E8, CanadaDepartment of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, CanadaDepartment of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, CanadaDepartment of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, CanadaInstitute of Animal Breeding and Genetics, University of Veterinary Medicine, 1210 Vienna, AustriaDepartment of Toxicology, University of Mainz Medical Center, 55131 Mainz, GermanyDepartment of Chemical & Physical Sciences, University of Toronto Mississauga, Mississauga, Ontario L5L 1C6, Canada; Department of Chemistry, University of Toronto, Toronto, Ontario M5S 2E8, CanadaHistone 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.https://www.explorationpub.com/Journals/etat/Article/1002166histone deacetylaseszinc-binding groupcap groupepigenetic regulationsmall-molecule inhibitorsmedicinal chemistry |
spellingShingle | Diaaeldin I. Abdallah Elvin D. de Araujo Naman H. Patel Lina S. Hasan Richard Moriggl Oliver H. Krämer Patrick T. Gunning Medicinal chemistry advances in targeting class I histone deacetylases Exploration of Targeted Anti-tumor Therapy histone deacetylases zinc-binding group cap group epigenetic regulation small-molecule inhibitors medicinal chemistry |
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 | histone deacetylases zinc-binding group cap group epigenetic regulation small-molecule inhibitors medicinal chemistry |
url | https://www.explorationpub.com/Journals/etat/Article/1002166 |
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