甲苯达唑是一种高效、广谱的抗线虫药。甲苯达唑对多形性乳腺母细胞瘤 (GBM) 也有抑制作用,抑制Hedgehog通路和微管蛋白 (tubulin) 聚合。甲苯达唑具有口服活性,可透过血脑屏障。
生物活性 | Mebendazole is a highly effective, broad-spectrum antihelmintic against nematode infestations. Mebendazole also exhibits inhibitory effect against glioblastoma multiforme (GBM), inhibitsHedgehogpathway andtubulinpolymerization. Mebendazole is orally active and can cross CNS penetration[1][2][3]. |
IC50& Target | Tublin polymerization[1]; Hedgehog[2]; Parasite[3] |
体外研究 (In Vitro) | Mebendazole (1 nM-0.1 mM; 72 h) shows inhibition of GL261 mouse glioma cells with IC value of 0.24 μM[1]. Mebendazole (0.1 μM and 1 μM; 24 h) disrupts microtubule polymerization and microtubule structure in 060919 glioblastoma multiforme (GBM) cells[1]. Mebendazole (10 nM-10 μM; 48 h) inhibits Hh signaling and reduces the expression of downstream Hh pathway effectors, by decreasingGli1transcript and protein expression in tumor tissues. Mebendazole inhibitsGli1expression with an IC50value of 516 nM[2]. Mebendazole (10 nM-10 μM; 48 h) prevents the formation of the primary cilium, and decreases the proliferation and survival of human medulloblastoma cells with constitutive Hh activation[2]. A combination of mebendazole andVismodegib(HY-10440) achieved additive inhibition of canonical Hh signaling[2]. Mebendazole has effectively treated CNS echinococcosis in numerous clinical settings before, indicating significant CNS penetration property[3].
Immunofluorescence[1] Cell Line: | Glioblastoma multiforme (GBM) 060919 cells | Concentration: | 1 μM | Incubation Time: | 24 hours | Result: | Disrupted microtubule structure. |
Immunofluorescence[2] Cell Line: | DAOY and hTERT-RPE1 cells | Concentration: | 0, 0.1, 0.5, 0.75, and 1 μM | Incubation Time: | 12 hours | Result: | Decreased GLI1 protein level and increased cleavage of caspase-3 protein level. |
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体内研究 (In Vivo) | Mebendazole (50 mg/kg; p.o.; once daily for first 20 d and 5 d per week with 2 d off; 45 d) inhibits intracranial tumor growth in the syngeneic GL261 mouse model and 060919 human glioblastoma multiforme (GBM) xenograft mouse model[1].
Animal Model: | C57BL/6 mice (5-6 weeks old) implanted with GL261 glioma cells and 060919 human glioblastoma multiforme (GBM)[1] | Dosage: | 50 mg/kg; delivered with 50% (v/v) sesame oil and PBS[2] | Administration: | Oral gavage; beginning 5 days after tumor implantation at a daily dose of 50 mg/kg for the first 20 days of treatment then changed to 50 mg/kg for 5 days, with 2 days off, each week. | Result: | Increased the mean survival to 49 days compared with the 30 days of control in syngeneic GL261 mouse model. Increased the mean survival to 65 days compared with the 48 days of control in 060919 human glioblastoma multiforme (GBM) xenograft mouse model. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 4.17 mg/mL(14.12 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic)(insoluble) 配制储备液 1 mM | 3.3865 mL | 16.9325 mL | 33.8650 mL | 5 mM | 0.6773 mL | 3.3865 mL | 6.7730 mL | 10 mM | 0.3387 mL | 1.6933 mL | 3.3865 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 0.42 mg/mL (1.42 mM); Clear solution
此方案可获得 ≥ 0.42 mg/mL (1.42 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 4.2 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 0.42 mg/mL (1.42 mM); Clear solution
此方案可获得 ≥ 0.42 mg/mL (1.42 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 4.2 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 0.42 mg/mL (1.42 mM); Clear solution
此方案可获得 ≥ 0.42 mg/mL (1.42 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 4.2 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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