Camptothecins in clinical development
Camptothecins in clinical development
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DOI：
10.1517/13543784.13.3.269
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发表时间：
2004-03
影响因子：
6.1
通讯作者：
F. Zunino;G. Pratesi
中科院分区：
文献类型：
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作者：
F. Zunino;G. Pratesi
在认识到DNA拓扑异构酶I是用于设计潜在抑制剂的有用的治疗靶标之后，拓扑异构酶I抑制剂现在代表了一类已建立的有效药剂。尽管在该领域进行了大量努力，但只有喜树碱具有临床相关性。天然喜树碱的化学操作的几种选择已被探索，以克服药物的主要缺点，其中包括水不溶性，内酯不稳定性，药物-靶点相互作用的可逆性和耐药性。几种类似物目前正在临床开发中，包括水溶性喜树碱、亲脂性喜树碱和聚合物结合的喜树碱。新型喜树碱类药物相对于已批准用于临床的两种类似物（拓扑替康和伊立替康）的治疗优势仍有待确定。本文概述了正在进行临床开发的类似物的相关特征。
Following the realisation that DNA topoisomerase I is a useful therapeutic target to be exploited for the design of potential inhibitors, topoisomerase I inhibitors now represent an established class of effective agents. In spite of intense efforts in the field, only camptothecins have a clinical relevance. Several options in chemical manipulation of natural camptothecin have been explored to overcome the major drawbacks of the drug, which include water insolubility, lactone instability, reversibility of the drug–target interaction and drug resistance. Several analogues are currently in clinical development, including water soluble camptothecins, lipophilic camptothecins and polymer-bound camptothecins. The therapeutic advantages of novel camptothecins over the two analogues (topotecan and irinotecan) approved for clinical use remain to be defined. This article is an overview of the relevant features of the analogues that are undergoing clinical development.