Salinosporamide natural products: Potent 20 S proteasome inhibitors as promising cancer chemotherapeutics.
Salinosporamide natural products: Potent 20 S proteasome inhibitors as promising cancer chemotherapeutics.
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DOI：
10.1002/anie.201000728
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发表时间：
2010-12-03
影响因子：
16.6
通讯作者：
Moore, Bradley S.
中科院分区：
文献类型：
--
作者：
Gulder, Tobias A. M.;Moore, Bradley S.
蛋白酶体抑制剂作为癌症治疗中有效的治疗选择正在迅速发展。这类药物中最有前景的候选药物之一是来自热带盐孢菌的沙利度胺A。这种海洋天然产物具有复杂的、高度官能化的γ-内酰胺 - β-内酯药效团，这是它与其靶点——20S蛋白酶体的β亚基不可逆结合的原因。沙利度胺A在被发现仅三年后就进入了治疗多发性骨髓瘤的I期临床试验。这种化合物强大的生物活性和具有挑战性的结构近年来激发了学术界和工业界的大量研究，这导致了十多种合成方法的开发、其生物合成途径的阐明以及有前景的构效关系和肿瘤学数据的产生。因此，沙利度胺A是现代药物发现与生物医学研究、药物化学与药理学、天然产物合成与分析以及生物合成与生物工程成功相互作用的一个有趣例子。
Proteasome inhibitors are rapidly evolving as potent treatment options in cancer therapy. One of the most promising drug candidates of this type is salinosporamide A from the bacterium Salinispora tropica. This marine natural product possesses a complex, densely functionalized γ-lactam-β-lactone pharmacophore, which is responsible for its irreversible binding to its target, the β subunit of the 20S proteasome. Salinosporamide A entered phase I clinical trials for the treatment of multiple myeloma only three years after its discovery. The strong biological activity and the challenging structure of this compound have fueled intense academic and industrial research in recent years, which has led to the development of more than ten syntheses, the elucidation of its biosynthetic pathway, and the generation of promising structure–activity relationships and oncological data. Salinosporamide A thus serves as an intriguing example of the successful interplay of modern drug discovery and biomedical research, medicinal chemistry and pharmacology, natural product synthesis and analysis, as well as biosynthesis and bioengineering.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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