Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy.
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.
Meng
Ling-Hua
LH
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Liao
Zhi-Yong
ZY
Pommier
Yves
Y
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors