Departments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai , New York, New York 10029, United States.
Chem Rev. 2018 Feb 14;118(3):989-1068. doi: 10.1021/acs.chemrev.6b00801. Epub 2017 Mar 24.
Post-translational modifications of histones by protein methyltransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene expression and transcription and are implicated in cancer and many other diseases. Many of these enzymes also target various nonhistone proteins impacting numerous crucial biological pathways. Given their key biological functions and implications in human diseases, there has been a growing interest in assessing these enzymes as potential therapeutic targets. Consequently, discovering and developing inhibitors of these enzymes has become a very active and fast-growing research area over the past decade. In this review, we cover the discovery, characterization, and biological application of inhibitors of PMTs and KDMs with emphasis on key advancements in the field. We also discuss challenges, opportunities, and future directions in this emerging, exciting research field.
组蛋白的翻译后修饰由蛋白质甲基转移酶（PMTs）和组蛋白去甲基化酶（KDMs）完成，在基因表达和转录的调控中发挥着重要作用，并且与癌症和许多其他疾病有关。这些酶中的许多还靶向各种非组蛋白蛋白，影响许多关键的生物学途径。鉴于它们的关键生物学功能和在人类疾病中的意义，评估这些酶作为潜在治疗靶点的兴趣日益浓厚。因此，在过去十年中，发现和开发这些酶的抑制剂已成为一个非常活跃和快速发展的研究领域。在这篇综述中，我们介绍了 PMTs 和 KDMs 抑制剂的发现、表征和生物学应用，重点介绍了该领域的主要进展。我们还讨论了这一新兴、令人兴奋的研究领域的挑战、机遇和未来方向。
