Histone deacetylase 6 inhibitors in Alzheimer's disease therapy: structure design and challenges

IF 2.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-06-26 DOI:10.1016/j.bmcl.2025.130318

Baiyun Dang , Hou Chen , Shiru Liu , Haijuan Liu , Zhiwen Kang , Zhen Yang , Weixia Yang , Jiadong Hu , Xin Chen

引用次数: 0

Abstract

Recently, histone deacetylases 6 (HDAC6) has been extensively studied for involvement in pathogenesis of central nervous system (CNS) diseases, especially for Alzheimer's disease (AD). A lot of literatures have disclosed that HDAC6 inhibitors (HDAC6is) are effective and promising in AD treatment. Though many HDAC6is were reported, only a handful of them displayed appropriate in vivo activities in models of neurological diseases. BBB permeability and off-target toxicity are the major obstacle and challenge for the development of available HDAC6is. In this review, we summarized recent brain-permeable HDAC6is from drug design perspective, and discussed the challenges and structural modification attempts in developing HDAC6is with better blood-brain barrier (BBB) permeability.

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阿尔茨海默病治疗中的组蛋白去乙酰化酶6抑制剂：结构设计和挑战

近年来，组蛋白去乙酰化酶6 （HDAC6）因参与中枢神经系统（CNS）疾病，特别是阿尔茨海默病（AD）的发病机制而被广泛研究。大量文献表明HDAC6抑制剂（HDAC6is）在阿尔茨海默病的治疗中是有效且有前景的。尽管报道了许多hdac6，但只有少数在神经系统疾病模型中显示出适当的体内活性。血脑屏障通透性和脱靶毒性是现有hdac6开发的主要障碍和挑战。本文从药物设计的角度对近年来脑通透性hdac6进行了综述，并讨论了开发具有更好血脑屏障（BBB）通透性的hdac6所面临的挑战和结构改造尝试。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.