Rafoxanide
(Synonyms: 雷复尼特) 目录号 : GC32683
An anthelmintic
Cas No.:22662-39-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Rafoxanide is an anthelmintic.1,2,3 In vivo, rafoxanide (50 mg/kg) completely eradicates E. caproni infection in mice.1 It is active against H. contortus in sheep when administered at a dose of 10 mg/kg and eliminates mature F. hepatica flukes in cattle when administered at a dose of 7.5 mg/kg.2,3 It is also cytotoxic to A375 and A431 skin cancer cells in vitro (IC50s = 10.9 and 1.31 ?M, respectively) and reduces tumor growth in an A375 mouse xenograft model when administered at a dose of 40 mg/kg.3 Formulations containing rafoxanide have been used in the treatment of parasitic infections in sheep and cattle.
1.K., M., Decere, M., and Fried, B.Effects of the anthelmintics clorsulon, rafoxanide, mebendazole and arprinocid on Echinostoma caproni in ICR miceJ. Helminthol.70(1)95-96(1996) 2.Egerton, J.R., Yakstis, J.J., and Campbell, W.C.Efficacy of rafoxanide (3,5-diiodo-3'-chloro-4'-(p-chlorophenoxy) salicylanilide) against Haemonchus contortus in sheepRes. Vet. Sci.11(4)382-388(1970) 3.Knapp, S.E., and Presidente, P.J.A.Efficacy of rafoxanide against natural fasciola hepatica infections in cattleAm. J. Vet. Res.32(8)1289-1291(1971)
| Cas No. | 22662-39-1 | SDF | |
| 别名 | 雷复尼特 | ||
| Canonical SMILES | O=C(NC1=CC=C(OC2=CC=C(Cl)C=C2)C(Cl)=C1)C3=CC(I)=CC(I)=C3O | ||
| 分子式 | C19H11Cl2I2NO3 | 分子量 | 626.01 |
| 溶解度 | DMSO : ≥ 31 mg/mL (49.52 mM) | 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 | 1.5974 mL | 7.9871 mL | 15.9742 mL |
| 5 mM | 0.3195 mL | 1.5974 mL | 3.1948 mL |
| 10 mM | 0.1597 mL | 0.7987 mL | 1.5974 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。
Rafoxanide sensitizes colorectal cancer cells to TRAIL-mediated apoptosis
Biomed Pharmacother 2022 Nov;155:113794.PMID:36271571DOI:10.1016/j.biopha.2022.113794.
Colorectal cancer (CRC) remains a leading causes of cancer-related death in the world, mainly due to the lack of effective treatment of advanced disease. TNF-related apoptosis-inducing ligand (TRAIL)-driven cell death, a crucial event in the control of tumor growth, selectively targets malignant rather than non-transformed cells. However, the fact that cancer cells, including CRC cells, are either intrinsically resistant or acquire resistance to TRAIL, represents a major hurdle to the use of TRAIL-based strategies in the clinic. Agents able to overcome CRC cell resistance to TRAIL have thus great therapeutic potential and many researchers are making efforts to identify TRAIL sensitizers. The anthelmintic drug Rafoxanide has recently emerged as a potent anti-tumor molecule for different cancer types and we recently reported that Rafoxanide restrained the proliferation of CRC cells, but not of normal colonic epithelial cells, both in vitro and in a preclinical model mimicking sporadic CRC. As these findings were linked with the induction of endoplasmic reticulum stress, a phenomenon involved in the regulation of various components of the TRAIL-driven apoptotic pathway, we sought to determine whether Rafoxanide could restore the sensitivity of CRC cells to TRAIL. Our data show that Rafoxanide acts as a selective TRAIL sensitizer in vitro and in a syngeneic experimental model of CRC, by decreasing the levels of c-FLIP and survivin, two key molecules conferring TRAIL resistance. Collectively, our data suggest that Rafoxanide could potentially be deployed as an anti-cancer drug in the combinatorial approaches aimed at overcoming CRC cell resistance to TRAIL-based therapies.
Repositioning Rafoxanide to treat Gram-negative bacilli infections
J Antimicrob Chemother 2020 Jul 1;75(7):1895-1905.PMID:32240294DOI:10.1093/jac/dkaa103.
Objectives: Repurposing drugs provides a new approach to the fight against MDR Gram-negative bacilli (MDR-GNB). Rafoxanide, a veterinary antihelminthic drug, has shown antibacterial activity in vitro against Gram-positive bacteria. We aimed to analyse the in vitro and in vivo efficacy of Rafoxanide in combination with colistin against colistin-susceptible (Col-S) and colistin-resistant (Col-R) GNB. Methods: A collection of Col-S and Col-R Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae were used. Chequerboard and time-kill curve analyses were performed to determine the synergy between Rafoxanide and colistin. Changes in membrane structure and permeability were analysed using transmission electron microscopy and fluorescence assays. A murine peritoneal sepsis model using Col-R strains of these pathogens was performed to study the efficacy of Rafoxanide (10 mg/kg/24 h, IV), colistimethate sodium (CMS) (20 mg/kg/8 h, intraperitoneally) and Rafoxanide (10 mg/kg/24 h, IV) plus CMS (20 mg/kg/8 h, intraperitoneally) for 72 h. Results: Rafoxanide showed MICs ≥256 mg/L for all Col-S and Col-R strains. Chequerboard and time-kill curve analyses showed that Rafoxanide (1 mg/L) is more synergistic with colistin against Col-R than Col-S strains. Col-R, but not Col-S, strains treated with Rafoxanide demonstrated higher membrane permeabilization. Transmission electron microscopy visualization confirmed that Col-R strains suffer morphological changes. In the murine peritoneal sepsis model with Col-R strains, Rafoxanide plus CMS, compared with CMS alone, increased mouse survival to 53.8% and 73.3%, and reduced bacterial loads in tissues and blood between 2.34 and 4.99 log10 cfu/g or mL, respectively. Conclusions: Rafoxanide repurposing, as monotherapy and in combination with CMS, may address the urgent need for new treatments for infections caused by MDR-GNB.
Rafoxanide Induces Immunogenic Death of Colorectal Cancer Cells
Cancers (Basel) 2020 May 21;12(5):1314.PMID:32455811DOI:10.3390/cancers12051314.
Colorectal cancer (CRC) is a major cause of cancer-related death in the world. Emerging evidence suggests that the clinical success of conventional chemotherapy does not merely rely on cell toxicity, but also results from the restoration of tumor immune surveillance. Anti-tumor immune response can be primed by immunogenic cell death (ICD), a form of apoptosis associated with endoplasmic reticulum stress (ERS) induction and the expression/release of specific damage-associated molecular patterns (DAMPs). Unfortunately, a limited number of ICD inducers have been identified so far. The anti-helmintic drug Rafoxanide has recently showed anti-tumor activity in different cancer types, including CRC. As such latter effects relied on ERS activation, we here investigated whether Rafoxanide could promote ICD of CRC cells. The potential of Rafoxanide to induce ICD-related DAMPs in both human and mouse CRC cells was assessed by flow-cytometry, chemiluminescent assay and ELISA. In addition, the immunogenic potential of Rafoxanide was assessed in vivo using a vaccination assay. Rafoxanide induced all the main DAMPs (ecto-calreticulin exposure, adenosine triphosphate (ATP)/high mobility group box 1 (HMGB1) release) required for ICD. We observed a marked increase of tumor-free survival among immunocompetent mice immunized with rafoxanide-treated dying tumor cells as compared with sham. Altogether, our data indicate Rafoxanide as a bona fide ICD inducer.
Rafoxanide promotes apoptosis and autophagy of gastric cancer cells by suppressing PI3K /Akt/mTOR pathway
Exp Cell Res 2019 Dec 15;385(2):111691.PMID:31678170DOI:10.1016/j.yexcr.2019.111691.
Rafoxanide is commonly used as anti-helminthic medicine in veterinary medicine, a main compound of salicylanilide. Previous studies have reported that Rafoxanide, as an inhibitor of BRAF V600E mutant protein, inhibits the growth of colorectal cancer, multiple myeloma, and skin cancer. However, its therapeutic effect on gastric cancer (GC) and the potential mechanism has not been investigated. Here, we have found that Rafoxanide inhibited the proliferation of GC cells in vitro, arrested the cell cycle in the G0/G1 phase, and promoted apoptosis and autophagy in GC cells. Treatment with specific autophagy inhibitor 3-methyladenine drastically inhibited the apoptotic cell death effect by suppressing the switch from autophagy to apoptosis. Mechanistically, we found that Rafoxanide inhibited the growth of GC cells in vitro by inhibiting the activity of the PI3K/Akt/mTOR signaling pathway. This process induced autophagy, which essentially resulted in the apoptosis of GC cells. Results from subcutaneous implanted tumor models in nude mice also indicated that Rafoxanide inhibited the growth of GC cells in vivo. Taken together, our findings revealed that Rafoxanide inhibited the growth of GC cells both in vitro and vivo, indicating a potential drug candidate for the treatment of GC.
Discovery of Rafoxanide as a novel agent for the treatment of non-small cell lung cancer
Sci Rep 2023 Jan 13;13(1):693.PMID:36639421DOI:10.1038/s41598-023-27403-y.
Non-small cell lung cancer (NSCLC), which accounts for approximately 85% of all lung cancer cases, is associated with a poor outcome. Rafoxanide is an anthelmintic drug that inhibits tumor growth in certain malignancies. However, its impact on NSCLC remains unknown. In this study, we examined the effect of Rafoxanide on NSCLC and dissected the underlying mechanism. The results showed that Rafoxanide significantly inhibited the growth, invasion, and migration of NSCLC cells. Besides, Rafoxanide can induce NSCLC cell apoptosis and cell cycle arrest in a dose-dependent manner. RNA-seq analysis revealed that genes associated with endoplasmic reticulum stress (ER) stress responses were activated. Mechanistically, we found Rafoxanide can induce ER stress and activate the unfolded protein response (UPR). Apoptosis was activated by excessive ER stress, and autophagy was activated to partially alleviate ER stress. In vivo, we found that Rafoxanide inhibited the growth of A549 and H1299 xenograft mouse models without severe side effects. Collectively, the present study indicates that Rafoxanide may be a candidate drug for the treatment of NSCLC.