甲苯咪唑（1 nM-0.1 mM；72 小时）抑制 GL261 肿瘤神经细胞，IC50 值为 0.24 μM [1]。 0.1 μM 和 1 μM 甲苯咪唑作用 24 小时会导致 060919 多形性星形胶质细胞破坏。甲苯咪唑（10 nM–10 μM；48 小时）抑制肿瘤 (GBM) 细胞中的微管聚合和微管结构，抑制 Hh 信号传导，并减少下游 Hh 蛋白表达。它还通过降低肿瘤组织中的 Gli1 来调节 Hh 蛋白的表达 [1]。 Gli1 表达受甲硝唑抑制，IC50 值为 516 nM[2]。当暴露于甲苯咪唑（10 nM-10 μM；48 小时）时，具有组成型 Hh 激活的人髓母细胞瘤肿瘤细胞表现出表达降低并阻碍初级纤毛发育。当甲苯咪唑和维莫德吉联合使用时，可以实现对正常 Hh 信号传导的加性抑制 [2]。在治疗环境中，甲苯咪唑已被证明可以成功治疗严重的中枢神经系统包虫病病例。荧光成像 [1]

对人多形性母细胞瘤 (GBM) 异种移植物 060919 和同基因 GL261 小鼠模型均给予甲苯咪唑（50 mg/kg；口服；前 20 天每天一次，每周 5 天，休息两天；45 天）。

免疫荧光 [1]
细胞类型： 多形性胶质母细胞瘤 (GBM) 060919 细胞
测试浓度： 1 μM
孵育时间：24小时
实验结果：微管结构被破坏。系统渗透特性[3]。

---

免疫荧光 [2]
细胞类型： DAOY 和 hTERT-RPE1 细胞
测试浓度： 0、0.1、0.5、0.75 和1 μM
孵育持续时间：12 小时
实验结果：GLI1 蛋白水平降低，caspase-3 蛋白水平增加裂解。

Animal/Disease Models: C57BL/6 mice (5-6 weeks old) implanted with GL261 glioma cells and 060919 human glioblastoma multiforme (GBM) [1]
Doses: 50 mg/kg; Inhibition in mouse model Intracranial tumor growth [1]. Use 50% (v/v) sesame oil and PBS[2]
Route of Administration: po (oral gavage); starting 5 days after tumor implantation, daily dose of 50 mg/kg for the first 20 days of treatment, then changing to 50 mg/kg, Lasts 5 days, with 2 days off per week.
Experimental Results: In the syngeneic GL261 mouse model, mean survival increased to 49 days compared with 30 days in controls. Mean survival was extended to 65 days compared with 48 days of controls in the 060919 human glioblastoma multiforme (GBM) xenograft mouse model.

Absorption, Distribution and Excretion
This product is poorly absorbed in the gastrointestinal tract (approximately 5%–10%). Fatty foods can increase absorption. In the human body, approximately 2% of mebendazole is excreted in the urine, and the remainder is excreted in the feces as the unchanged drug or its major metabolite. Excretion: Feces: Approximately 95% is excreted in the feces as the unchanged drug or its major metabolite (2-amino derivative). Kidneys: Approximately 2%–5% is excreted in the urine as the unchanged drug or its major metabolite. Peak serum concentration: After 3 days of twice-daily administration of 100 mg: Mebendazole: Not exceeding 0.03 μg/mL. 2-Amino metabolite: Not exceeding 0.09 μg/mL. It has been reported that serum concentrations can reach 0.5 μg/mL during long-term high-dose treatment. Time to peak serum concentration: 2 to 5 hours (range: 0.5 to 7 hours). Mebendazole is highly bound to plasma proteins. It is currently unclear whether mebendazole is excreted into breast milk. For more complete data on the absorption, distribution, and excretion of mebendazole (11 items total), please visit the HSDB record page. Metabolites/Metabolic Substances Primarily metabolized in the liver. The major metabolite is 2-amino-5-benzoylbenzimidazole, but it is also metabolized to inactive hydroxy and hydroxyamino metabolites. None of the metabolites have anthelmintic activity. Primarily metabolized in the liver; metabolized to inactive amino, hydroxy, and hydroxyamino metabolites; the major metabolite is 2-amino-5-benzoylbenzimidazole. Although the exact metabolic pathway of mebendazole is not fully determined, the drug is decarboxylated to 2-amino-5(6)-benzimidazolylphenyl ketone; this metabolite has no anthelmintic activity. Mebendazole…is widely metabolized. The two main metabolites, 5-(α-5-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5-benzoylbenzimidazole, have lower clearance rates than mebendazole itself. Mebendazole, rather than its metabolites, appears to be the active drug form. Conjugates of mebendazole and its metabolites have been found in bile, but almost no unmetabolized mebendazole is found in urine.
Biological Half-Life
The biological half-life in patients with normal liver function is 2.5 to 5.5 hours (range 2.5 to 9 hours). The biological half-life in patients with impaired liver function (cholestasis) is approximately 35 hours.
Normal liver function: 2.5 to 5.5 hours (range: 2.5 to 9 hours). Impaired liver function (cholestasis): approximately 35 hours.
The elimination half-life of mebendazole has been reported to be approximately 2.8–9 hours.

Hepatotoxicity
Mebendazole typically does not cause elevated serum enzymes at conventional doses, although treatment duration is usually short and reports of enzyme elevation are rare. High-dose treatment (rarely used now due to the advent of albendazole) can lead to elevated serum transaminase levels (2 to 10 times the normal value), but is generally well tolerated. Rare reports of acute liver injury caused by mebendazole exist, especially with repeated or high-dose administration. Onset usually occurs within days of starting or restarting treatment, presenting as fever and malaise. The pattern of elevated serum enzymes is usually hepatocellular, and jaundice is uncommon. These abnormalities usually resolve rapidly after discontinuation of the drug. Typical manifestations of allergic reactions (rash, fever, and eosinophilia) and liver biopsy may show granulomas.
Probability score: D (Long-term treatment may lead to clinically significant liver injury).
Use during pregnancy and lactation

◉ Overview of use during lactation
Mebendazole is rarely excreted into breast milk and is poorly absorbed orally. Reports on mebendazole use during lactation show no adverse reactions in breastfed infants. A few cases have reported reduced milk production after mebendazole use, but there is no conclusive evidence that this is caused by the drug. No special attention is required.
◉ Effects on Breastfed Infants
A case series reported on 45 lactating women who took mebendazole at doses ranging from 100 mg once daily to 200 mg twice daily for 3 days. Approximately half of the infants received 100 mg, repeated once after 7 to 14 days. 33 infants were exclusively breastfed, aged 1 to 30 weeks. Of the 12 partially breastfed infants, 8 were over 20 weeks old. None of the mothers reported any adverse reactions.
In the Democratic Republic of Congo, researchers followed up on 33 infants (the extent of breastfeeding was not specified) breastfed by mothers hospitalized and taking nifurolimus. Thirty mothers completed a course of 30 doses of oral nifurolimus (15 mg/kg/day), and all mothers received 14 doses of intravenous efornithine (400 mg/kg/day) for 7 days to treat human African trypanosomiasis (sleeping sickness). Seventeen lactating mothers also received mebendazole. No serious adverse events were reported in any of the breastfed infants.
◉ Effects on lactation and breast milk
A lactating mother 13 weeks postpartum was taking metronidazole 250 mg three times daily. Milk production appeared unaffected. On the eighth day of treatment, she expelled a roundworm. Metronidazole was discontinued, and mebendazole was started at 100 mg twice daily. The patient felt “stressed” for several days after expelling the roundworm. On the second day of mebendazole treatment, milk production decreased significantly, and she began adding formula. By the seventh day, milk production had completely stopped. The authors suggest that mebendazole may be the cause of decreased milk production, but provide no further evidence beyond the time frame. Four patients received mebendazole at 100 mg twice daily for three days, starting on postpartum day. Two were infected with Enterobius, one with Ascaris, and one with Ancyclostomia. All subjects successfully breastfed. One author reported that information obtained through private communication with the manufacturer indicated no milk suppression was observed in lactating mothers after a single oral dose of 100 mg mebendazole (postpartum time not specified). In a case series study, 45 lactating mothers received mebendazole at doses ranging from 100 mg once daily to 200 mg twice daily for three days. One mother reported a slight decrease in milk production. Protein Binding Rate: 90-95% Drug Interactions: Preliminary evidence suggests that cimetidine inhibits the metabolism of mebendazole and may lead to elevated plasma drug concentrations. Limited data indicate that both carbamazepine and phenytoin sodium may enhance the metabolism of mebendazole, possibly by inducing hepatic microsomal enzymes, resulting in decreased plasma mebendazole concentrations. This interaction is unlikely to be clinically significant in treated patients. Mebendazole is used to treat intestinal worm infections; however, in patients receiving mebendazole for extraintestinal infections (e.g., echinococcosis), concomitant use of carbamazepine or phenytoin sodium may affect its efficacy. Until more data are available, other anticonvulsants (e.g., valproic acid) should be considered for patients receiving mebendazole for extraintestinal infections. Non-human Toxicity Values: Oral LD50 in sheep > 80 mg/kg

[1]. Bai RY, et al. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme. Neuro Oncol. 2011 Sep;13(9):974-82.
[2]. Larsen AR, et al. Repurposing the antihelmintic mebendazole as a hedgehog inhibitor. Mol Cancer Ther. 2015 Jan;14(1):3-13.
[3]. Erdinçler P, et al. The role of mebendazole in the surgical treatment of central nervous system hydatid disease. Br J Neurosurg. 1997 Apr;11(2):116-20.

Therapeutic Uses

MeSH Title: Antinematode Drugs
Mebendazole is indicated for the treatment of whipworm infection caused by Trichuris trichiura. /Included on US product label/
Mebendazole is indicated for the treatment of various intestinal nematode infections. /Included on US product label/
Mebendazole is indicated for the treatment of pinworm infection caused by Enterobius vermicularis. /Included on US product label/
For more complete data on the therapeutic uses of mebendazole (19 in total), please visit the HSDB record page.

---

Drug Warnings
During prolonged use of mebendazole, organ system function (including hematopoietic and liver function) should be evaluated regularly. Other rare adverse reactions in patients treated with mebendazole include alopecia, rash, pruritus, urticaria, angioedema, flushing, hiccups, cough, fatigue, somnolence, chills, hypotension, seizures, transient abnormalities in liver function tests (e.g., elevated serum transaminases, alkaline phosphatase, and/or bilirubin levels), hepatitis, elevated blood urea nitrogen, decreased hemoglobin levels and/or hematocrit, leukopenia, thrombocytopenia, eosinophilia, and hyperurea nitrogenosis. Urine columnar urination has also been reported. Ascaris lumbricoides migration via the mouth and nose has also been reported. Myelosuppression, manifested as neutropenia (including agranulocytosis) and/or thrombocytopenia, has been reported in patients receiving high doses (e.g., 30–50 mg/kg daily) of mebendazole for extraintestinal infections; although myelosuppression is usually reversible upon discontinuation of the drug, deaths are rare. At the commonly recommended dose (i.e., 100-200 mg daily), mebendazole appears to cause very few side effects. Side effects appear to be more common at higher doses (e.g., doses used to treat extraintestinal infections such as echinococcosis), and in some cases may be related to drug-induced parasite-killing effects. Transient diarrhea and abdominal pain have been occasionally reported during mebendazole treatment, but are usually associated with large amounts of infection and worm expulsion. Nausea, vomiting, headache, tinnitus, numbness, and dizziness have been occasionally reported during mebendazole treatment. Fever has occurred in some patients, especially those receiving high doses for extraintestinal infections. For more complete data on drug warnings for mebendazole (9 of 9), please visit the HSDB record page.

---

Pharmacodynamics
Mebendazole is a (synthetic) broad-spectrum anthelmintic. The primary mechanism of action of mebendazole is through the inhibition of tubulin polymerization, leading to the loss of cytoplasmic microtubules.

C16H13N3O3

295.3

295.095

31431-39-7

Mebendazole-d3;1173021-87-8

4030

Off-white amorphous powder
Crystals from acetic acid and methanol

1.4±0.1 g/cm3

288.5°C

1.703

2.83

84.08

2

4

4

22

423

0

O=C(OC)NC1=NC2=CC=C(C(C3=CC=CC=C3)=O)C=C2N1

OPXLLQIJSORQAM-UHFFFAOYSA-N InChi Code

InChI=1S/C16H13N3O3/c1-22-16(21)19-15-17-12-8-7-11(9-13(12)18-15)14(20)10-5-3-2-4-6-10/h2-9H,1H3,(H2,17,18,19,21)

methyl N-(6-benzoyl-1H-benzimidazol-2-yl)carbamate

Mebendazole Vermox Telmin Pantelmin Mebenvet Telmin Vermicol Vermidil Vermin Vermox Wormkuur

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~4.17 mg/mL (~14.12 mM)
H2O : < 0.1 mg/mL

配方 1 中的溶解度: ≥ 0.42 mg/mL (1.42 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 4.2 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 0.42 mg/mL (1.42 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 4.2mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 0.42 mg/mL (1.42 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 4.2 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。