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...

Full description

Bibliographic Details
Main Authors: Diaaeldin I. Abdallah, Elvin D. de Araujo, Naman H. Patel, Lina S. Hasan, Richard Moriggl, Oliver H. Krämer, Patrick T. Gunning
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2023-08-01
Series:Exploration of Targeted Anti-tumor Therapy
Subjects:
Online Access:https://www.explorationpub.com/Journals/etat/Article/1002166
_version_ 1827823728718774272
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
work_keys_str_mv AT diaaeldiniabdallah medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT elvinddearaujo medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT namanhpatel medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT linashasan medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT richardmoriggl medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT oliverhkramer medicinalchemistryadvancesintargetingclassihistonedeacetylases
AT patricktgunning medicinalchemistryadvancesintargetingclassihistonedeacetylases