组蛋白赖氨酸去甲基酶（KDMs）抑制剂的药物发现（2018 年至今的进展）。
Drug discovery of histone lysine demethylases (KDMs) inhibitors (progress from 2018 to present).
机构信息
School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
出版信息
Eur J Med Chem. 2022 Mar 5;231:114143. doi: 10.1016/j.ejmech.2022.114143. Epub 2022 Jan 20.
Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) play an important role in the regulation of gene expression, which implicates the development of various human cancers and other diseases. Discovering and developing inhibitors targeting KDMs have become an active and fast-growing research area over the past decades. In this review, the latest emerging small-molecule inhibitors of KDMs were surveyed with the emphasis on the literature since 2018, including lysine specific demethylases (LSD or KDM1) inhibitors and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7) inhibitors. The drug design strategy, the structure-activity relationships (SARs), the analysis and insight of co-crystal structures, and the mechanisms of action (MOA) were also discussed.
组蛋白的翻译后修饰（PTMs）由组蛋白去甲基酶（KDMs）完成，在基因表达的调控中起着重要作用，这暗示了各种人类癌症和其他疾病的发展。在过去几十年中，发现和开发针对 KDMs 的抑制剂已成为一个活跃且快速发展的研究领域。在这篇综述中，调查了最新出现的 KDMs 的小分子抑制剂，重点是 2018 年以后的文献，包括赖氨酸特异性去甲基酶（LSD 或 KDM1）抑制剂和 JmjC 家族 N-甲基赖氨酸去甲基酶（JmjC KDMs，即 KDM2-7）抑制剂。还讨论了药物设计策略、构效关系（SAR）、共晶结构的分析和见解，以及作用机制（MOA）。
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