Intoplicine is a pyrido[4,3-b]indole derivative patented by Rhone-Poulenc Sante as an antitumor agent. Intoplicine acts via inhibiting DNA nicking and closing reactions by stabilizing the cleavable complex, a transient intermediate in the religation reaction involving topoisomerase I and II and DNA. Intoplicine was active in a range of solid tumors in mice, including colon adenocarcinoma 51, MA16/C, MA14/A, MA13/C, early-stage pancreatic ductal adenocarcinoma 03, Glasgow osteogenic sarcoma and B16 melanoma. In Phase I clinical studies using a 24-h infusion, the maximum tolerated dose was established as 270 mg/m2 every 3 weeks, with hepatotoxicity rather than myelosuppression being dose-limiting, although cardiac toxicity was also seen. Preclinical cytotoxic concentrations were not achieved at the dose levels studied and clinical development was discontinued.