Abstract
Human DNA topoisomerase I is the target of camptothecins, which have been recently introduced in the clinic for cancer chemotherapy. The discovery of novel non-camptothecin inhibitors is facilitated by the availability of biochemical and cellular assays for testing topoisomerase I activity. Among the non-camptothecin inhibitors, the indolocarbazoles (NB-506 and J-107088) are the most advanced in their development, and are in clinical trials. A number of indenoisoquinolines and minor groove binders (benzimidazoles) have been reported recently. Their antitumor activity is promising for further development. The potential binding site(s) of topoisomerase I inhibitors in the enzyme I-DNA complex is discussed.
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