Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec, Poland.
Department of Pharmacognosy, University of Vienna, Vienna, Austria.
Nat Rev Drug Discov. 2021 Mar;20(3):200-216. doi: 10.1038/s41573-020-00114-z. Epub 2021 Jan 28.
Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.
天然产物及其结构类似物在历史上为药物治疗做出了重大贡献,尤其是在癌症和传染病方面。然而,天然产物也给药物发现带来了挑战,例如筛选、分离、鉴定和优化方面的技术障碍,这导致制药行业从 20 世纪 90 年代开始减少对它们的追求。近年来,一些技术和科学的发展——包括改进的分析工具、基因组挖掘和工程策略,以及微生物培养的进步——正在解决这些挑战,并开辟新的机遇。因此,人们对天然产物作为药物先导的兴趣正在重新焕发活力,特别是在解决抗微生物药物耐药性方面。在这里,我们总结了最近能够实现基于天然产物的药物发现的技术发展,重点介绍了一些应用,并讨论了关键机遇。