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kahalalides在癌症控制应用中的最新进展与局限性

Recent advances and limitations in the application of kahalalides for the control of cancer.

作者信息

Wyer Scott, Townsend Danyelle M, Ye Zhiwei, Kourtidis Antonis, Choo Yeun-Mun, de Barros André Luís Branco, Donia Mohamed S, Hamann Mark T

机构信息

Department of Drug Discovery and Biomedical Science, College of Pharmacy, Medical University of South Carolina, Charleston 29425-5700, USA.

Department of Drug Discovery and Biomedical Science, College of Pharmacy, Medical University of South Carolina, Charleston 29425-5700, USA.

出版信息

Biomed Pharmacother. 2022 Apr;148:112676. doi: 10.1016/j.biopha.2022.112676. Epub 2022 Feb 8.

Abstract

Since the discovery of the kahalalide family of marine depsipeptides in 1993, considerable work has been done to develop these compounds as new and biologically distinct anti-cancer agents. Clinical trials and laboratory research have yielded a wealth of data that indicates tolerance of kahalalides in healthy cells and selective activity against diseased cells. Currently, two molecules have attracted the greates level of attention, kahalalide F (KF) and isokahalalide F (isoKF, Irvalec, PM 02734, elisidepsin). Both compounds were originally isolated from the sarcoglossan mollusk Elysia rufescens but due to distinct structural characteristics it has been hypothesized and recently shown that the ultimate origin of the molecules is microbial. The search for their true source has been a subject of considerable research in the anticipation of finding new analogs and a culturable expression system that can produce sufficient material through fermentation to be industrially relevant.

摘要

自1993年发现海洋缩肽类kahalalide家族以来,为将这些化合物开发成新型且具有独特生物学特性的抗癌药物,人们开展了大量工作。临床试验和实验室研究已产生了大量数据,这些数据表明kahalalides在健康细胞中具有耐受性,且对病变细胞具有选择性活性。目前,有两种分子引起了极大关注,即kahalalide F(KF)和异kahalalide F(isoKF、Irvalec、PM 02734、elisidepsin)。这两种化合物最初均从裸鳃亚目软体动物红海天牛中分离得到,但由于其独特的结构特征,有人推测并于近期证实这些分子的最终来源是微生物。寻找它们的真正来源一直是大量研究的主题,以期找到新的类似物以及一种可培养的表达系统,该系统能够通过发酵产生足够数量的物质,从而具有工业应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12fa/9004612/c4db7bf68185/nihms-1793767-f0001.jpg

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