Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization

@article{Rose2006NovelFC,
  title={Novel fluoro-substituted camptothecins: in vivo antitumor activity, reduced gastrointestinal toxicity and pharmacokinetic characterization},
  author={William C. Rose and Punit H. Marathe and Graham R. Jang and Thomas M. Monticello and Balu N Balasubramanian and Byron H. Long and Craig R. Fairchild and Monroe E. Wall and Mansukh C. Wani},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2006},
  volume={58},
  pages={73-85}
}
  • W. RoseP. Marathe M. Wani
  • Published 1 July 2006
  • Biology, Chemistry, Medicine
  • Cancer Chemotherapy and Pharmacology
Purpose: The novel fluoro-substituted camptothecin analog, BMS-286309, and its prodrug, BMS-422461, were evaluated for their pharmacologic, toxicologic, metabolic and pharmacokinetic developmental potential. Methods: In vitro and in vivo assays were used to assess the compounds for topoisomerase I activity, antitumor activity, gastrointestinal (GI) toxicity, and pharmacokinetic parameters. Results: BMS-286309-induced topoisomerase I-mediated DNA breaks in vitro and was similar in potency to… 

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