Targeting histone deacetylase 1: Inhibition and activation as promising therapeutic strategies for diverse disorders

IF 5.9 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2025-07-23 DOI:10.1016/j.ejmech.2025.117998

Giuliana Costanzo, Rocco Buccheri, Giuseppe Cosentino, Carlo Reale, Sara Zuccalà, Agostino Marrazzo, Emanuele Amata, Antonio Rescifina, Lorella Pasquinucci

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Abstract

Epigenetic regulation plays a crucial role in several pathological conditions. Dysregulation of histone deacetylase (HDAC) enzymes has been implicated in the onset and progression of numerous diseases, including cancer, inflammatory disorders, and neurodegenerative conditions. Most known HDAC inhibitors (HDACi) are classified as “pan-inhibitors”, targeting multiple HDAC isoforms indiscriminately. However, the growing demand for isoform-selective ligands has emphasized the need for more targeted therapeutic strategies. Among HDAC isoforms, HDAC1 has emerged as a particularly promising target for pharmacological intervention. This review provides a comprehensive overview of current HDAC1-selective ligands, including inhibitors and activators, highlighting their potential as useful therapeutic tools. The most promising class I of HDACi currently in clinical trials is discussed.

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靶向组蛋白去乙酰化酶1：抑制和激活作为多种疾病的有希望的治疗策略

表观遗传调控在几种病理条件下起着至关重要的作用。组蛋白去乙酰化酶（HDAC）酶的失调与许多疾病的发生和进展有关，包括癌症、炎症性疾病和神经退行性疾病。大多数已知的HDAC抑制剂（HDACi）被归类为“泛抑制剂”，不加区别地靶向多种HDAC亚型。然而，对异构体选择性配体日益增长的需求强调了对更有针对性的治疗策略的需求。在HDAC异构体中，HDAC1已成为一个特别有希望的药物干预靶点。这篇综述提供了目前hdac1选择性配体的全面概述，包括抑制剂和激活剂，强调了它们作为有用治疗工具的潜力。讨论了目前临床试验中最有前途的一类HDACi。

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.