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.

Fontana, A., Cursaro, I., Carullo, G., Gemma, S., Butini, S., Campiani, G. (2022). A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(17), 1-43 [10.3390/ijms231710014].

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

Fontana A.;Cursaro I.;Carullo G.;Gemma S.;Butini S.
;
Campiani G.
2022

Abstract

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.
Fontana, A., Cursaro, I., Carullo, G., Gemma, S., Butini, S., Campiani, G. (2022). A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(17), 1-43 [10.3390/ijms231710014].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/1216359