From plant to cancer drug: lessons learned from the discovery of taxol

IF 10.2 1区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Natural Product Reports Pub Date : 2023-01-01 DOI:10.1039/d3np00017f
Nadja B. Cech , Nicholas H. Oberlies
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引用次数: 1

Abstract

Many researchers in the natural product sciences dream of discovering a successful drug. For almost all of us, this dream will never be realized. Among the heroes of our past, though, there is a team whose efforts led to the discovery of not one but two new drugs. Dr Monroe Wall and Dr Mansukh Wani isolated and solved the structures for taxol and camptothecin, plant-based compounds that continue to play a critical role in cancer therapy today. Since the 1960s and 1970s when Wall, Wani and collaborators did their seminal work, there have been tremendous technological advances in the natural product sciences. With access to most sophisticated technology, it might be expected that the rate of discovery of new drugs from plants and other sources would have sped up. However, this has not come to pass. Why is this? Is it that the promise of new drug candidates from plant-based sources has been exhausted? Has our fascination with new technologies and with the promise of the genomics revolution caused us to stop investing effort and resources in the practices that are proven to yield success? With this Viewpoint, we share the story of taxol's discovery, highlighting critical challenges that were overcome and considering their relevance to botanical natural products drug discovery today. We hope that consideration of lessons learned from the past will help fuel success by researchers currently studying plants with the goal of discovering promising therapeutic leads.

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从植物到癌症药物:紫杉醇发现的经验教训
自然产品科学领域的许多研究人员梦想着发现一种成功的药物。对我们几乎所有人来说,这个梦想永远不会实现。然而,在我们过去的英雄中,有一个团队的努力发现了两种新药,而不是一种。Monroe Wall博士和Mansukh Wani博士分离并解决了紫杉醇和喜树碱的结构,这两种植物化合物至今仍在癌症治疗中发挥着关键作用。自20世纪60年代和70年代Wall、Wani及其合作者进行了开创性的工作以来,自然产品科学取得了巨大的技术进步。随着获得最先进的技术,从植物和其他来源发现新药的速度可能会加快。然而,这并没有实现。为什么会这样?植物来源的候选新药的前景是否已经破灭?我们对新技术和基因组学革命的承诺的迷恋是否导致我们停止在被证明会取得成功的实践中投入精力和资源?通过这一观点,我们分享了紫杉醇的发现故事,强调了所克服的关键挑战,并考虑到它们与当今植物天然产物药物发现的相关性。我们希望,对过去经验教训的思考将有助于推动目前研究植物的研究人员取得成功,目的是发现有前景的治疗线索。
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来源期刊
Natural Product Reports
Natural Product Reports 化学-生化与分子生物学
CiteScore
21.20
自引率
3.40%
发文量
127
审稿时长
1.7 months
期刊介绍: Natural Product Reports (NPR) serves as a pivotal critical review journal propelling advancements in all facets of natural products research, encompassing isolation, structural and stereochemical determination, biosynthesis, biological activity, and synthesis. With a broad scope, NPR extends its influence into the wider bioinorganic, bioorganic, and chemical biology communities. Covering areas such as enzymology, nucleic acids, genetics, chemical ecology, carbohydrates, primary and secondary metabolism, and analytical techniques, the journal provides insightful articles focusing on key developments shaping the field, rather than offering exhaustive overviews of all results. NPR encourages authors to infuse their perspectives on developments, trends, and future directions, fostering a dynamic exchange of ideas within the natural products research community.
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