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

J Med Chem. 2005 Apr 7;48(7):2258-61. doi: 10.1021/jm049090z.

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.

Publication types

  • Comparative Study

MeSH terms

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

Substances

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