Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642)

Desirée Hao, Jinee D. Rizzo, Stephanie Stringer, Rodney V. Moore, Jennifer Marty, Daniel L. Dexter, Gina L. Mangold, James B. Camden, Daniel D. Von Hoff, Steven D. Weitman

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Methyl-2-benzimidazolecarbamate (carbendazim, FB642) is an anticancer agent that induces apoptosis of cancer cells. In vitro, FB642 demonstrated potent antitumor activity against both the murine B16 melanoma (IC50 = 8.5 μm) and human HT-29 colon carcinoma (IC50 = 9.5 μm) cell lines. FB642 was also highly active against both murine tumor models and human tumor xenografts at varying doses and schedules. In the murine B 16 melanoma model, T/C values > 200 were observed. In the human tumor xenograft, FB642 produced tumor growth inhibition of greater than 58% in five of the seven xenograft models evaluated. Partial and complete tumor shrinkage was noted with FB642 against the MCF-7 breast tumor model. Pharmacokinetic studies in rats demonstrated that oral absorption of FB642 was variable and may be saturated at the 2000 mg/kg dose level since higher doses failed to produce a further increase in the area under the time concentration curve. Toxicity of FB642 in vivo appeared to be dose-dependent. Lower doses in the range of 2000-3000 mg/kg were better tolerated, while still preserving antitumor activity. Evaluation of FB642 in phase I clinical trials of adult patients with advanced malignancies is currently ongoing.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalInvestigational New Drugs
Volume20
Issue number3
DOIs
StatePublished - Aug 8 2002

Keywords

  • Benzimidazole carbamates
  • FB642
  • Preclinical pharmacology

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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