Abstract
Methyl-2-benzimidazolecarbamate(carbendazim, FB642) is an anticancer agentthat induces apoptosis of cancer cells. Invitro, FB642 demonstrated potent antitumoractivity against both the murine B16melanoma (IC50 = 8.5 μm) andhuman HT-29 colon carcinoma(IC50 = 9.5 μm) cell lines. FB642was also highly active against both murinetumor models and human tumor xenografts atvarying doses and schedules. In the murineB16 melanoma model, T/C values > 200 wereobserved. In the human tumor xenograft,FB642 produced tumor growth inhibition ofgreater than 58% in five of the sevenxenograft models evaluated. Partial andcomplete tumor shrinkage was noted withFB642 against the MCF-7 breast tumor model.Pharmacokinetic studies in ratsdemonstrated that oral absorption of FB642was variable and may be saturated at the2000 mg/kg dose level since higher dosesfailed to produce a further increase in thearea under the time concentration curve. Toxicity of FB642 in vivo appeared to bedose-dependent. Lower doses in the range of2000–3000 mg/kg were better tolerated,while still preserving antitumor activity. Evaluation of FB642 in phase I clinicaltrials of adult patients with advancedmalignancies is currently ongoing.
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Hao, D., Rizzo, J.D., Stringer, S. et al. Preclinical Antitumor Activity and Pharmacokinetics of Methyl-2-Benzimidazolecarbamate (FB642). Invest New Drugs 20, 261–270 (2002). https://doi.org/10.1023/A:1016253716438
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DOI: https://doi.org/10.1023/A:1016253716438