组蛋白脱乙酰基酶
医学
表观遗传学
临床试验
疾病
生物信息学
药理学
糖尿病
不利影响
组蛋白脱乙酰酶抑制剂
重新调整用途
肾脏疾病
组蛋白
生物
内科学
内分泌学
遗传学
基因
生态学
作者
Mitchell J. Hadden,Andrew Advani
摘要
Despite recent clinical trial advances and improvements in clinical care, kidney disease due to diabetes remains the most common cause of chronic kidney failure worldwide. In the search for new treatments, recent attentions have turned to drug repurposing opportunities, including study of the histone deacetylase (HDAC) inhibitor class of agents. HDACs are a group of enzymes that remove functional acetyl groups from histone and non-histone proteins and they can affect cellular function through both epigenetic and non-epigenetic means. Over the past decade, several HDAC inhibitors have been adopted into clinical practice, primarily for the treatment of hematological malignancy, whereas other existing therapies (for instance valproate) have been found to have HDAC inhibitory effects. Here we review the current HDAC inhibitors in the clinic and under development; the literature evidence supporting the renoprotective effects of HDAC inhibitors in experimental diabetic kidney disease; and the adverse effect profiles that may prevent existing therapies from entering the clinic for this indication. Whereas recent research efforts have shed light on the fundamental actions of HDACs in the diabetic kidney, whether these efforts will translate into novel therapies for patients will require more specific and better-tolerated therapies.
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