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
Institute for Drug Development, Cancer Therapy and Research Center, San Antonio 78245-3217, USA.
Invest New Drugs. 2002 Aug;20(3):261-70. doi: 10.1023/a:1016253716438.
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 microm) and human HT-29 colon carcinoma (IC50 = 9.5 microm) cell lines. FB642 was also highly active against both murine tumor models and human tumor xenografts at varying doses and schedules. In the murine B16 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 2,000-3,000 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.
甲基-2-苯并咪唑氨基甲酸酯（多菌灵，FB642）是一种可诱导癌细胞凋亡的抗癌剂。在体外，FB642对小鼠B16黑色素瘤细胞系（IC50 = 8.5微摩尔）和人HT-29结肠癌细胞系（IC50 = 9.5微摩尔）均显示出强大的抗肿瘤活性。FB642在不同剂量和给药方案下对小鼠肿瘤模型和人肿瘤异种移植物也具有高度活性。在小鼠B16黑色素瘤模型中，观察到T/C值> 200。在人肿瘤异种移植物中，在评估的七个异种移植物模型中的五个中，FB642产生了大于58%的肿瘤生长抑制。在MCF-7乳腺肿瘤模型中，FB642导致肿瘤部分和完全缩小。大鼠的药代动力学研究表明，FB642的口服吸收存在差异，在2000 mg/kg剂量水平可能达到饱和，因为更高剂量未能使时间浓度曲线下面积进一步增加。FB642在体内的毒性似乎呈剂量依赖性。2000-3000 mg/kg范围内的较低剂量耐受性较好，同时仍保留抗肿瘤活性。目前正在对患有晚期恶性肿瘤的成年患者进行FB642的I期临床试验评估。
