Title: Non-Camptothecin DNA Topoisomerase I Inhibitors in Cancer Therapy
Volume: 3
Issue: 3
Author(s): Meng Ling-hua, Liao Zhi-yong and Yves Pommier
Affiliation:
Keywords:
dna topoisomerases, topoisomerase II, anticancer drugs, dna cleavage, dna ligation, dna cleavage complex
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 noncamptothecin 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.
