Class I HDAC Inhibitors: Potential New Epigenetic Therapeutics for Alcohol Use Disorder (AUD),Journal of Medicinal Chemistry

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Class I HDAC Inhibitors: Potential New Epigenetic Therapeutics for Alcohol Use Disorder (AUD)
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-08-22 00:00:00 , DOI: 10.1021/acs.jmedchem.7b00115
Erika Bourguet _{1,

2} , Katarzyna Ozdarska _{1,

3} , Gautier Moroy ₄ , Jérôme Jeanblanc _{2,

5} , Mickaël Naassila _{2,

5}

Affiliation

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.

中文翻译：

I类HDAC抑制剂：酒精使用障碍（AUD）的潜在新表观遗传学治疗药物

饮酒障碍（AUD）代表着严重的公共卫生问题，迫切需要发现新疗法。酒精暴露已被广泛证明可部分地通过组蛋白脱乙酰基酶（HDAC）抑制来调节表观遗传机制，例如组蛋白乙酰化/脱乙酰化平衡。已建议表观遗传因素在澳元中起关键作用。迄今为止，已鉴定出18种不同的哺乳动物HDAC同工型，并将其分为四类。由于最近的研究表明，基于AUD的表观遗传机制以及AUD的不同动物模型中HDAC抑制剂（HDACIs）的功效均可能涉及I类HDAC，因此我们在此报告了I类HDACI的发展，包括有关其结构，效力，和选择性。需要付出更多的努力来提高选择性，

更新日期：2017-08-23

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