Rizvi Noreen F, Smith Graham F
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
AstraZeneca, Darwin Building, 310 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.
Bioorg Med Chem Lett. 2017 Dec 1;27(23):5083-5088. doi: 10.1016/j.bmcl.2017.10.052. Epub 2017 Oct 23.
Small molecule drugs have readily been developed against many proteins in the human proteome, but RNA has remained an elusive target for drug discovery. Increasingly, we see that RNA, and to a lesser extent DNA elements, show a persistent tertiary structure responsible for many diverse and complex cellular functions. In this digest, we have summarized recent advances in screening approaches for RNA targets and outlined the discovery of novel, drug-like small molecules against RNA targets from various classes and therapeutic areas. The link of structure, function, and small-molecule Druggability validates now for the first time that RNA can be the targets of therapeutic agents.
小分子药物已很容易针对人类蛋白质组中的许多蛋白质开发出来，但RNA仍然是药物发现中难以捉摸的靶点。我们越来越多地看到，RNA以及程度稍轻的DNA元件呈现出一种持久的三级结构，这种结构负责许多多样而复杂的细胞功能。在本综述中，我们总结了RNA靶点筛选方法的最新进展，并概述了针对来自各类别和治疗领域的RNA靶点发现新型、类药物小分子的情况。结构、功能与小分子可成药性之间的联系首次证实RNA可以成为治疗药物的靶点。
