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 language | English (US) |
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Pages (from-to) | 261-270 |
Number of pages | 10 |
Journal | Investigational New Drugs |
Volume | 20 |
Issue number | 3 |
DOIs | |
State | Published - 2002 |
Keywords
- Benzimidazole carbamates
- FB642
- Preclinical pharmacology
ASJC Scopus subject areas
- Oncology
- Pharmacology
- Pharmacology (medical)