Dual Topo III Inhibitors

A number of drugs have been identified that simultaneously target both topo I and topo II.10 Interest in these compounds is based on observations that the timing of expression of topo I and topo II differs, with topo II levels at their highest during S phase, while levels of topo I remain relatively constant through the cell cycle.152 Cellular resistance to topo I inhibitors is often accompanied by a concomitant rise in the level of topo II and vice versa, since expression of either enzyme appears to be sufficient to support cell division.153 While it is still not clear how viable this concept is, some of these compounds show high activity in preclinical tests, and in some cases suggestions of novel mechanisms of action, although it is difficult to decide whether both activities contribute to the cytotoxicity.10

7.05.4.1 Camptothecins

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