Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Trends Pharmacol Sci. 2018 Oct;39(10):855-866. doi: 10.1016/j.tips.2018.07.005. Epub 2018 Aug 22.
Across disease indications, there is immediate need for new drug targets. Target scarcity is reflected in a growing number of same-target drugs of marginal clinical value. Advances in RNA mechanisms of disease are revealing a windfall of targets for nucleic acids therapeutics. However, nucleic acids remain limited as pharmaceutical agents. Because enzymes are predominant drug targets, ribonucleases represent an established target class to capitalize on RNA mechanisms of disease. Analysis of the human proteome identified 122 ribonucleases. This small ribonucleome mediates the biosynthetic and catabolic processing of a large transcriptome. Thus, ribonucleases represent critical signaling targets. Similar to kinases, proteases, and epigenetic enzymes, ribonucleases are rational targets for development of therapies with novel mechanisms, expanding treatment options for improved patient outcomes.
在各种疾病的治疗中，我们迫切需要新的药物靶点。靶点稀缺反映在大量临床价值有限的同靶点药物不断增加。疾病的 RNA 机制的研究进展揭示了大量核酸治疗药物靶点。然而，核酸在药物研发中仍然受到限制。由于酶是主要的药物靶点，核糖核酸酶代表了利用疾病的 RNA 机制的一个既定的靶点类别。对人类蛋白质组的分析确定了 122 种核糖核酸酶。这个小的核糖核酶组介导了大量转录组的生物合成和分解代谢处理。因此，核糖核酸酶是关键的信号靶点。与激酶、蛋白酶和表观遗传酶类似，核糖核酸酶是开发具有新机制的治疗方法的合理靶点，为改善患者预后提供了更多的治疗选择。
