喜树碱
拓扑替康
伊立替康
拓扑异构酶
前药
药理学
药效学
药代动力学
医学
化学
癌症
酶
化疗
内科学
生物化学
结直肠癌
作者
Diederik F. S. Kehrer,Otto Soepenberg,Walter J. Loos,Jaap Verweij,Alex Sparreboom
出处
期刊:Anti-Cancer Drugs
[Ovid Technologies (Wolters Kluwer)]
日期:2001-02-01
卷期号:12 (2): 89-105
被引量:109
标识
DOI:10.1097/00001813-200102000-00002
摘要
The topoisomerase I inhibitors reviewed in this paper are all semisynthetic analogs of camptothecin (CPT). Modulation of this intranuclear enzyme translates clinically in to antitumor activity against a broad spectrum of tumors and is therefore the subject of numerous investigations. We present preclinical and clinical data on CPT analogs that are already being used in clinical practice [i.e. topotecan and irinotecan (CPT-11)] or are currently in clinical development (e.g. 9-aminocamptothecin, 9-nitrocamptotecin, lurtotecan, DX 8951f and BN 80915), as well as drugs that are still only developed in a preclinical setting (silatecans, polymer-bound derivates). A variety of different strategies is being used to modulate the systemic delivery of this class of agents, frequently in order to increase antitumor activity and/or reduce experienced side effects. Three principal approaches are discussed, including: (i) pharmaceutical modulation of formulation vehicles, structural alterations and the search for more water-soluble prodrugs, (ii) modulation of routes of administration and considerations on infusion duration, and (iii) both pharmacodynamic and pharmacokinetic biomodulation.
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