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 journalArticle

30 Citations (Scopus)

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 - 2002

Fingerprint

Pharmacokinetics
Neoplasms
Heterografts
Inhibitory Concentration 50
carbendazim
Experimental Melanomas
Clinical Trials, Phase I
Antineoplastic Agents
Melanoma
Appointments and Schedules
Colon
Apoptosis
Breast Neoplasms
Carcinoma
Cell Line
Growth

Keywords

  • Benzimidazole carbamates
  • FB642
  • Preclinical pharmacology

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Hao, D., Rizzo, J. D., Stringer, S., Moore, R. V., Marty, J., Dexter, D. L., ... Weitman, S. D. (2002). Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642). Investigational New Drugs, 20(3), 261-270. https://doi.org/10.1023/A:1016253716438

Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642). / Hao, Desirée; Rizzo, Jinee D.; Stringer, Stephanie; Moore, Rodney V.; Marty, Jennifer; Dexter, Daniel L.; Mangold, Gina L.; Camden, James B.; Von Hoff, Daniel D.; Weitman, Steven D.

In: Investigational New Drugs, Vol. 20, No. 3, 2002, p. 261-270.

Research output: Contribution to journalArticle

Hao, D, Rizzo, JD, Stringer, S, Moore, RV, Marty, J, Dexter, DL, Mangold, GL, Camden, JB, Von Hoff, DD & Weitman, SD 2002, 'Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642)', Investigational New Drugs, vol. 20, no. 3, pp. 261-270. https://doi.org/10.1023/A:1016253716438
Hao, Desirée ; Rizzo, Jinee D. ; Stringer, Stephanie ; Moore, Rodney V. ; Marty, Jennifer ; Dexter, Daniel L. ; Mangold, Gina L. ; Camden, James B. ; Von Hoff, Daniel D. ; Weitman, Steven D. / Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642). In: Investigational New Drugs. 2002 ; Vol. 20, No. 3. pp. 261-270.
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