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

  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},
  • 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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Metabolic and Pharmaceutical Aspects of Fluorinated Compounds.

The literature associated with the metabolism of fluorinated molecules is summarized, focusing on examples where the presence of fluorine influences the metabolic profile.

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  • 2011
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  • Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2001
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  • G. Chabot
  • Biology, Medicine
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  • 1997
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  • T. BurkeZ. Mi
  • Chemistry, Biology
    Journal of medicinal chemistry
  • 1994
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Identification of a new metabolite of CPT-11 (irinotecan): pharmacological properties and activation to SN-38.

The structure of CPT-11, a water-soluble derivative of camptothecine with promising activity against several types of malignancies, is postulated to be 7-ethyl-10-(4-amino-1-piperidino)carbonyloxycamptotheCine, and this structure was synthesized by Rhône-Poulenc Rorer.

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Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities.

The rational design and total synthesis of highly lipophilic A,B,E- ring-modified camptothecins that are the most blood- stable camptotcin-class topoisomerase I inhibitors displaying intrinsic anticancer activity yet to be identified are described.