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A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors

Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged...

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Autores principales: Fontana, Anna, Cursaro, Ilaria, Carullo, Gabriele, Gemma, Sandra, Butini, Stefania, Campiani, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456347/
https://www.ncbi.nlm.nih.gov/pubmed/36077415
http://dx.doi.org/10.3390/ijms231710014
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author Fontana, Anna
Cursaro, Ilaria
Carullo, Gabriele
Gemma, Sandra
Butini, Stefania
Campiani, Giuseppe
author_facet Fontana, Anna
Cursaro, Ilaria
Carullo, Gabriele
Gemma, Sandra
Butini, Stefania
Campiani, Giuseppe
author_sort Fontana, Anna
collection PubMed
description Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators.
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spelling pubmed-94563472022-09-09 A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors Fontana, Anna Cursaro, Ilaria Carullo, Gabriele Gemma, Sandra Butini, Stefania Campiani, Giuseppe Int J Mol Sci Review Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators. MDPI 2022-09-02 /pmc/articles/PMC9456347/ /pubmed/36077415 http://dx.doi.org/10.3390/ijms231710014 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fontana, Anna
Cursaro, Ilaria
Carullo, Gabriele
Gemma, Sandra
Butini, Stefania
Campiani, Giuseppe
A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title_full A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title_fullStr A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title_full_unstemmed A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title_short A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
title_sort therapeutic perspective of hdac8 in different diseases: an overview of selective inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456347/
https://www.ncbi.nlm.nih.gov/pubmed/36077415
http://dx.doi.org/10.3390/ijms231710014
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