Rebeccamycin

Indolocarbazoles are another group of topoiso-merase-I inhibitors, of which rebeccamycin, a naturally occurring anti-tumor antibiotic, derived from an actinomycete. In addition to their action on DNA, rebeccamycin analogues may inhibit the SR kinase activity of topoisomerase I and therefore constitute a unique family of topoisomerase-I poisons quite different from the well-known camptothecins (Prud-homme 2000). In vitro studies support activity in neuroblastoma (Weitman et al. 1998; Marminon et al. 2003). Dose-limiting toxicity in both adults and children in phase-1 studies was myelosuppression (Dowlati et al. 2001; Langevin et al. 2003). A phase-II study in pediatric solid tumors is currently ongoing at MSKCC and in the COG.

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