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) |
|---|---|
| Pages (from-to) | 261-270 |
| Number of pages | 10 |
| Journal | Investigational New Drugs |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2002 |
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Keywords
- Benzimidazole carbamates
- FB642
- Preclinical pharmacology
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Preclinical antitumor activity and pharmacokinetics of methyl-2-benzimidazolecarbamate (FB642)
AU - Hao, Desirée
AU - Rizzo, Jinee D.
AU - Stringer, Stephanie
AU - Moore, Rodney V.
AU - Marty, Jennifer
AU - Dexter, Daniel L.
AU - Mangold, Gina L.
AU - Camden, James B.
AU - Von Hoff, Daniel D.
AU - Weitman, Steven D
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Benzimidazole carbamates
KW - FB642
KW - Preclinical pharmacology
UR - http://www.scopus.com/inward/record.url?scp=0036021202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036021202&partnerID=8YFLogxK
U2 - 10.1023/A:1016253716438
DO - 10.1023/A:1016253716438
M3 - Article
C2 - 12201489
AN - SCOPUS:0036021202
VL - 20
SP - 261
EP - 270
JO - Investigational New Drugs
JF - Investigational New Drugs
SN - 0167-6997
IS - 3
ER -