Discovery of a fluoroindolo[2,3-a]carbazole clinical candidate with broad spectrum antitumor activity in preclinical tumor models superior to the marketed oncology drug, CPT-11.

Abstract

A series of fluoroglycosylated fluoroindolocarbazoles was examined with respect to their topoisomerase I activity, cytotoxicity, and selectivity. The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, including curative antitumor activity against Lewis lung carcinoma.

• Authors: Mark G Saulnier, Balu N Balasubramanian, Byron H Long, David B Frennesson, Edward Ruediger, Kurt Zimmermann, Jeffrey T Eummer, Denis R St Laurent, Karen M Stoffan, B Narasimhulu Naidu, Mikael Mahler, Francis Beaulieu, Carol Bachand, Frank Y Lee, Craig R Fairchild, Linda K Stadnick, William C Rose, Carola Solomon, Henry Wong, Alain Martel, John J Wright, Robert Kramer, David R Langley, Dolatrai M Vyas
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 48 Issue 7 Pg. 2258-61 (Apr 07 2005) ISSN: 0022-2623 [Print] United States
• PMID: 15801816 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• BMS 250749
• Carbazoles
• Glucosides
• Indoles
• Topoisomerase I Inhibitors
• Irinotecan
• Camptothecin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Camptothecin (analogs & derivatives, pharmacology)
• Carbazoles (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Drug Evaluation, Preclinical
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Glucosides (chemical synthesis, chemistry, pharmacology)
• Humans
• In Vitro Techniques
• Indoles (chemical synthesis, chemistry, pharmacology)
• Irinotecan
• Mice
• Microsomes, Liver (metabolism)
• Topoisomerase I Inhibitors
• Transplantation, Heterologous