Parbendazole (SKF 29044)
(Synonyms: 帕苯咪唑,SKF 29044) 目录号 : GC32134
An inhibitor of microtubule assembly
Cas No.:14255-87-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | Pure tubulin is obtained from sheep brain by 2 cycles of assembly and disassembly in vitro. Immediately prior to use the protein is centrifuged at 130000 g for 30 min to remove any aggregates. It is used at a protein concentration of 0-2 mg/mL in 0.025 M Pipes buffer, 0-5 mM EGTA, 0-25 mM Mg2SOsup>4, 0.1 mM GTP. Drug binding is determined by equilibrium dialysis using concentrations of parbendazole between 0.1 μM and 4 μM, and 2% (v/v) DMF (dimethyl formamide) as a carrier. Equilibrium is achieved by constant stirring for 2 h at 26°C, bovine serum albumin being used as a standard. 200 μL aliquots are counted in PCS in a 25-200B liquid scintillation counter[2]. |
Cell experiment: | Vero cells, an established cell line derived from monkey kidney are seeded in DMEM supplemented with 10% (v/v) foetal calf serum onto glass coverslips in multiwell dishes. They are allowed to settle, and spread for 2-5 h in a humid atmosphere at 37°C. After this time the medium is changed to DMEM containing 2, 10 or 20 μM parbendazole and 1% (v/v) DMSO controls contained 1 % (v/v) DMSO or had no additions[2]. |
References: [1]. Lo YC, et al. Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential. Sci Rep. 2017 Sep 12;7(1):11261. | |
Parbendazole is an inhibitor of microtubule assembly (EC50 = 3 ?M).1 It reduces viability of HeLa cells (EC50 = 0.53 ?M) and induces genotoxic stress in a reporter assay using HEK293 cells.2 Parbendazole reduces, but does not eradicate, worm burden in goats with naturally acquired or experimental nematode infections when administered at a dose of 15 mg/kg.3 It is teratogenic to lamb embryos when administered to pregnant ewes at a dose of 60 mg/kg during the third week of pregnancy.
1.Havercroft, J.C., Quinlan, R.A., and Gull, K.Binding of parbendazole to tubulin and its influence on microtubules in tissue-culture cells as revealed by immunofluorescence microscopyJ. Cell Sci.49195-204(1981) 2.Lo, Y.-C., Senese, S., France, B., et al.Computational cell cycle profiling of cancer cells for prioritizing FDA-approved drugs with repurposing potentialSci. Rep.7(1)(2017) 3.Charles, T.P., Pompeu, J., and Miranda, D.B.Efficacy of three broad-spectrum anthelmintics against gastrointestinal nematode infections of goatsVet. Parasitol.34(1-2)71-75(1989)
| Cas No. | 14255-87-9 | SDF | |
| 别名 | 帕苯咪唑,SKF 29044 | ||
| Canonical SMILES | O=C(OC)NC1=NC2=CC=C(CCCC)C=C2N1 | ||
| 分子式 | C13H17N3O2 | 分子量 | 247.29 |
| 溶解度 | DMSO : 4 mg/mL (16.18 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0438 mL | 20.2192 mL | 40.4384 mL |
| 5 mM | 0.8088 mL | 4.0438 mL | 8.0877 mL |
| 10 mM | 0.4044 mL | 2.0219 mL | 4.0438 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
The Antitumor Potentials of Benzimidazole Anthelmintics as Repurposing Drugs
Immune Netw 2020 Aug 4;20(4):e29.PMID:32895616DOI:10.4110/in.2020.20.e29.
The development of refractory tumor cells limits therapeutic efficacy in cancer by activating mechanisms that promote cellular proliferation, migration, invasion, metastasis, and survival. Benzimidazole anthelmintics have broad-spectrum action to remove parasites both in human and veterinary medicine. In addition to being antiparasitic agents, benzimidazole anthelmintics are known to exert anticancer activities, such as the disruption of microtubule polymerization, the induction of apoptosis, cell cycle (G2/M) arrest, anti-angiogenesis, and blockage of glucose transport. These antitumorigenic effects even extend to cancer cells resistant to approved therapies and when in combination with conventional therapeutics, enhance anticancer efficacy and hold promise as adjuvants. Above all, these anthelmintics may offer a broad, safe spectrum to treat cancer, as demonstrated by their long history of use as antiparasitic agents. The present review summarizes central literature regarding the anticancer effects of benzimidazole anthelmintics, including albendazole, Parbendazole, fenbendazole, mebendazole, oxibendazole, oxfendazole, ricobendazole, and flubendazole in cancer cell lines, animal tumor models, and clinical trials. This review provides valuable information on how to improve the quality of life in patients with cancers by increasing the treatment options and decreasing side effects from conventional therapy.
Connectivity Map-based discovery of Parbendazole reveals targetable human osteogenic pathway
Proc Natl Acad Sci U S A 2015 Oct 13;112(41):12711-6.PMID:26420877DOI:10.1073/pnas.1501597112.
Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. In this study, we have identified pathways that stimulate differentiation of bone forming osteoblasts from human mesenchymal stromal cells (hMSCs). Gene expression profiling was performed in hMSCs differentiated toward osteoblasts (at 6 h). Significantly regulated genes were analyzed in silico, and the Connectivity Map (CMap) was used to identify candidate bone stimulatory compounds. The signature of Parbendazole matches the expression changes observed for osteogenic hMSCs. Parbendazole stimulates osteoblast differentiation as indicated by increased alkaline phosphatase activity, mineralization, and up-regulation of bone marker genes (alkaline phosphatase/ALPL, osteopontin/SPP1, and bone sialoprotein II/IBSP) in a subset of the hMSC population resistant to the apoptotic effects of Parbendazole. These osteogenic effects are independent of glucocorticoids because Parbendazole does not up-regulate glucocorticoid receptor (GR) target genes and is not inhibited by the GR antagonist mifepristone. Parbendazole causes profound cytoskeletal changes including degradation of microtubules and increased focal adhesions. Stabilization of microtubules by pretreatment with Taxol inhibits osteoblast differentiation. Parbendazole up-regulates bone morphogenetic protein 2 (BMP-2) gene expression and activity. Cotreatment with the BMP-2 antagonist DMH1 limits, but does not block, parbendazole-induced mineralization. Using the CMap we have identified a previously unidentified lineage-specific, bone anabolic compound, Parbendazole, which induces osteogenic differentiation through a combination of cytoskeletal changes and increased BMP-2 activity.
Identification of anthelmintic Parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning
Acta Pharm Sin B 2022 May;12(5):2429-2442.PMID:35646536DOI:10.1016/j.apsb.2021.12.005.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out Parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of Parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic Parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.
Binding of Parbendazole to tubulin and its influence on microtubules in tissue-culture cells as revealed by immunofluorescence microscopy
J Cell Sci 1981 Jun;49:195-204.PMID:7031071DOI:10.1242/jcs.49.1.195.
We have shown that the benzimidazole carbamate, Parbendazole, is a potent inhibitor of microtubule assembly in vitro and in vivo. Radiolabelled Parbendazole was shown to bind to purified tubulin. Immunofluorescence studies using antitubulin antibody showed that Parbendazole effectively depolymerizes cytoplasmic microtubules in animal cells leaving only one or two microtubules associated with one centriole. The usefulness of Parbendazole and other benzimidazole carbamates as inhibitors of microtubule functions is discussed.
Structural insights into targeting of the colchicine binding site by ELR510444 and Parbendazole to achieve rational drug design
RSC Adv 2021 May 25;11(31):18938-18944.PMID:35478655DOI:10.1039/d1ra01173a.
Microtubules consisting of α- and β-tubulin heterodimers have proven to be an efficient drug target for cancer therapy. A broad range of agents, including ELR510444 and Parbendazole, can bind to tubulin and interfere with microtubule assembly. ELR510444 and Parbendazole are colchicine binding site inhibitors with antiproliferative activities. However, the lack of structural information on the tubulin-ELR510444/Parbendazole complex has hindered the design and development of more potent drugs with similar scaffolds. Therefore, we report the crystal structures of tubulin complexed with ELR510444 at a resolution of 3.1 Å and with Parbendazole at 2.4 Å. The structure of these complexes revealed the intermolecular interactions between the two colchicine binding site inhibitors and tubulin, thus providing a rationale for the development of novel benzsulfamide and benzimidazole derivatives targeting the colchicine binding site.