Class I HDAC Inhibitors: Potential New Epigenetic Therapeutics for Alcohol Use Disorder (AUD)
Class I HDAC Inhibitors: Potential New Epigenetic Therapeutics for Alcohol Use Disorder (AUD)
复制标题
I类组蛋白去乙酰化酶抑制剂：酒精使用障碍（AUD）潜在的新型表观遗传疗法
DOI：
10.1021/acs.jmedchem.7b00115
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发表时间：
2018-03-08
影响因子：
7.3
通讯作者：
Naassila, Mickael
中科院分区：
文献类型：
--
作者：
Bourguet, Erika;Ozdarska, Katarzyna;Naassila, Mickael
酒精使用障碍（AUD）是一个严重的公共卫生问题，发现新的治疗方法是迫切需要的。酒精暴露已被广泛证明可以调节表观遗传机制，如组蛋白乙酰化/脱乙酰化平衡，部分通过组蛋白脱乙酰酶（HDAC）抑制。表观遗传因素已被认为在AUD中起关键作用。迄今为止，已经鉴定了18种不同的哺乳动物HDAC同种型，并且这些已被分为四类。由于最近的研究表明，AUD的表观遗传机制和HDAC抑制剂（HDACIs）在不同的AUD动物模型中的疗效可能涉及I类HDAC，我们在此报告了I类HDACIs的发展，包括有关其结构，效力和选择性的信息。需要更多的努力来改善HDACIs的选择性，药代动力学和毒性特征，以更好地了解它们在减少成瘾行为方面的功效。
Alcohol use disorder (AUD) represents a serious public health issue, and discovery of new therapies is a pressing necessity. Alcohol exposure has been widely demonstrated to modulate epigenetic mechanisms, such as histone acetylation/deacetylation balance, in part via histone deacetylase (HDAC) inhibition. Epigenetic factors have been suggested to play a key role in AUD. To date, 18 different mammalian HDAC isoforms have been identified, and these have been divided into four classes. Since recent studies have suggested that both epigenetic mechanisms underlying AUD and the efficacy of HDAC inhibitors (HDACIs) in different animal models of AUD may involve class I HDACs, we herein report the development of class I HDACIs, including information regarding their structure, potency, and selectivity. More effort is required to improve the selectivity, pharmacokinetics, and toxicity profiles of HDACIs to achieve a better understanding of their efficacy in reducing addictive behavior.