Eukaryotic ribosome and cap-dependent translation are attractive targets in the antitumor, antiviral, anti-inflammatory, and antiparasitic therapies. Currently, a broad array of small-molecule drugs is known that specifically inhibit protein synthesis in eukaryotic cells. Many of them are well-studied ribosome-targeting antibiotics that block translocation, the peptidyl transferase center or the polypeptide exit tunnel, modulate the binding of translation machinery components to the ribosome, and induce miscoding, premature termination or stop codon readthrough. Such inhibitors are widely used as anticancer, anthelmintic and antifungal agents in medicine, as well as fungicides in agriculture. Chemicals that affect the accuracy of stop codon recognition are promising drugs for the nonsense suppression therapy of hereditary diseases and restoration of tumor suppressor function in cancer cells. Other compounds inhibit aminoacyl-tRNA synthetases, translation factors, and components of translation-associated signaling pathways, including mTOR kinase. Some of them have antidepressant, immunosuppressive and geroprotective properties. Translation inhibitors are also used in research for gene expression analysis by ribosome profiling, as well as in cell culture techniques. In this article, we review well-studied and less known inhibitors of eukaryotic protein synthesis (with the exception of mitochondrial and plastid translation) classified by their targets and briefly describe the action mechanisms of these compounds. We also present a continuously updated database (http://eupsic.belozersky.msu.ru/) that currently contains information on 370 inhibitors of eukaryotic protein synthesis.

中文翻译：

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真核蛋白质合成小分子抑制剂快速指南

真核核糖体和帽依赖性翻译是抗肿瘤、抗病毒、抗炎和抗寄生虫治疗中有吸引力的靶点。目前，已知有多种小分子药物可特异性抑制真核细胞中的蛋白质合成。其中许多是经过充分研究的核糖体靶向抗生素，可阻断易位、肽基转移酶中心或多肽出口通道，调节翻译机制成分与核糖体的结合，并诱导错误编码、提前终止或终止密码子通读。这种抑制剂在医学上被广泛用作抗癌剂、驱虫剂和抗真菌剂，以及在农业上用作杀菌剂。影响终止密码子识别准确性的化学物质是用于遗传性疾病的无义抑制治疗和恢复癌细胞中的肿瘤抑制功能的有前途的药物。其他化合物抑制氨酰-tRNA 合成酶、翻译因子和翻译相关信号通路的成分，包括 mTOR 激酶。其中一些具有抗抑郁、免疫抑制和老年保护作用。翻译抑制剂还用于通过核糖体分析进行基因表达分析的研究，以及细胞培养技术。在本文中，我们回顾了研究充分但鲜为人知的真核蛋白质合成抑制剂（线粒体和质体翻译除外），按其靶标分类，并简要描述这些化合物的作用机制。