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深入了解杂环作为组蛋白修饰酶抑制剂的治疗效果,这些抑制剂针对癌症表观遗传途径。

An insight into therapeutic efficacy of heterocycles as histone-modifying enzyme inhibitors that targets cancer epigenetic pathways.

机构信息

Department of Chemistry, Indian Academy Degree College-Autonomous, Bengaluru, Karnataka, India.

P.G. Department of Chemistry, Vijaya College, Bengaluru, Karnataka, India.

出版信息

Chem Biol Drug Des. 2022 Nov;100(5):682-698. doi: 10.1111/cbdd.14135. Epub 2022 Sep 16.

Abstract

Histone-modifying enzymes are the key regulators involved in the post-translational modification of histone and non-histone. These enzymes are responsible for the epigenetic control of cellular functions. However, deregulation of the activity of these enzymes results in uncontrolled disorders such as cancer and inflammatory and neurological diseases. The study includes histone acetyltransferases, deacetylases, methyl transferases, demethylases, DNA methyl transferases, and their potent inhibitors which are in a clinical trial and used as medicinal drugs. The present review covers the heterocycles as target-specific inhibitors of histone-modifying enzyme, more specifically histone acetyltransferases. This review also confers more recent reports on heterocycles as potential HAT inhibitors covered from 2016 to 2022 and future perspectives of these heterocycles in epigenetic therapy.

摘要

组蛋白修饰酶是参与组蛋白和非组蛋白翻译后修饰的关键调节因子。这些酶负责细胞功能的表观遗传控制。然而,这些酶活性的失调会导致不受控制的疾病,如癌症以及炎症和神经疾病。本研究包括组蛋白乙酰转移酶、去乙酰化酶、甲基转移酶、去甲基化酶、DNA 甲基转移酶及其在临床试验中用作药物的有效抑制剂。本综述涵盖了作为组蛋白修饰酶,特别是组蛋白乙酰转移酶的靶标特异性抑制剂的杂环化合物。本综述还介绍了 2016 年至 2022 年期间杂环化合物作为潜在 HAT 抑制剂的最新报道,并展望了这些杂环化合物在表观遗传学治疗中的未来前景。

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