Cancer therapies utilizing the camptothecins: a review of the in vivo literature.
Cancer therapies utilizing the camptothecins: a review of the in vivo literature.
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DOI：
10.1021/mp900243b
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发表时间：
2010-04-05
影响因子：
4.9
通讯作者：
Simanek EE
中科院分区：
文献类型：
--
作者：
Venditto VJ;Simanek EE
这篇综述总结了喜树碱或其衍生物衍生的化疗药物的体内初步、临床前和临床评估。喜树碱是一种天然存在的五环喹啉生物碱，在多种细胞系中具有高细胞毒活性。该药物的主要局限性，包括在生理条件下溶解度差和无活性，阻碍了临床的充分利用。喜树碱以活性内酯形式和无活性水解羧酸形式保持平衡。活性内酯结合DNA拓扑异构酶I切割复合体，被认为是抑制DNA重组的单一活性位点，导致细胞凋亡。一系列的小分子喜树碱衍生物已经被开发出来，它们提高了溶解度、内酯稳定性和生物利用度，并取得了不同程度的成功。许多大分子药物也被描述为喜树碱共价或非共价附加，目的是改善溶解度和内酯稳定性，同时利用肿瘤生理学向肿瘤输送大剂量的药物，同时降低全身毒性。随着对药物传递和聚合物疗法的兴趣日益增加，预计会有更多的结构。本综述的目的是为其他对喜树碱治疗领域感兴趣的人总结相关文献，特别是在生物分布、给药方案和药代动力学方面，以期提供有用的比较数据来源。为此，只有体内数据可用的结构才被报道。该审查包括截至2009年年中已发表的英文报告。
This review summarizes the in vivo assessment--preliminary, preclinical, and clinical--of chemotherapeutics derived from camptothecin or a derivative. Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines. Major limitations of the drug, including poor solubility and inactivity at physiological conditions, prevent full clinical utilization. Camptothecin remains at equilibrium in an active lactone form and inactive hydrolyzed carboxylate form. The active lactone binds to DNA topoisomerase I cleavage complex, believed to be the single site of activity inhibiting DNA religation, resulting in apoptosis. A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success. A number of macromolecular agents have also been described wherein camptothecin(s) are covalently appended or non-covalently associated with the goal of improving solubility and lactone stability, while taking advantage of the tumor physiology to deliver larger doses of drug to the tumor with lower systemic toxicity. With the increasing interest in drug delivery and polymer therapeutics, additional constructs are anticipated. The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data. To this end, only constructs where in vivo data is available are reported. The review includes published reports in English through mid-2009.
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影响因子：
10.8
作者：
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通讯作者：
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影响因子：
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