Niclosamide (ethanolamine salt)
(Synonyms: 氯硝柳胺乙醇胺盐,BAY2353 olamine) 目录号 : GC44400
氯硝柳胺是一种经美国食品和药物管理局 (FDA) 批准用于治疗肠道蛔虫感染的驱虫药。
Cas No.:1420-04-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HeLa cells |
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Preparation Method |
Cells were plated in 96-well culture plates with cell density of 3000-4000 cells/well and treated with indicated compounds by adding 100µL medium containing Niclosamide (ethanolamine salt) of various concentrations on the second day. After 72-hour's treatment, MTT was added to each well and incubated for additional 4-5 hours, and the absorbance was measured on a microplate reader at 570nm. Cell growth inhibition was evaluated as the ratio of the absorbance of the sample to that of the control. |
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Reaction Conditions |
0.5-5µM for 72 hours |
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Applications |
Niclosamide dose dependently inhibited STAT3-dependent luciferase reporter activity with an IC50 of 0.25 ± 0.07 µM. |
| Animal experiment [2]: | |
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Animal models |
NOD/SCID mice |
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Preparation Method |
HCT116 cells were harvested from flasks with 0.05% trypsin/EDTA and resuspended with Hank's buffered solution (5 × 106 cells/100 µL). CRC explants (CRC039) cultured in vitro were harvested with the same procedure and mixed with equal volume of Matrigel to make 1 × 106 cells/100 µL concentration. The cell suspensions (100 µL) were inoculated into the flanks of NOD/SCID mice. Four days later, niclosamide administration by gavage 6 d/wk for 2 (HCT116) or 3 weeks (CRC039) began. Tumor size was measured 3 times a week until mice were euthanized. |
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Dosage form |
Niclosamide (10, 100, and 200 mg/kg) was administered by gavage for 6 d/wk for 2 (HCT116) or 3 weeks (CRC039). |
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Applications |
In the more rapidly growing tumor (HCT116), a dose of 200 mg/kg of body weight was needed to suppress the tumor growth; 100 mg/kg of niclosamide could suppress the growth of the relatively slow-growing tumor (CRC039) to the same level. |
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References: [1]: Ren X, Duan L, He Q, et al. Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway[J]. ACS medicinal chemistry letters, 2010, 1(9): 454-459. |
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Niclosamide is an anthelmintic drug approved by the US Food and Drug Administration (FDA) for treating intestinal infections of tapeworms [1,2]. The mechanism of action of the drug is to uncouple the mitochondria of the parasitic worms [1,2], and it has an excellent safety profile. Niclosamide (ethanolamine salt) is a salt form of niclosamide that has higher water solubility [1-3].
Niclosamide dose dependently inhibited STAT3-dependent luciferase reporter activity with an IC50 of 0.25 ± 0.07 μM [4]. Niclosamide inhibits Wnt/Frizzled signalling induced by the complete agonist (Wnt) with IC50 of 0.5 ± 0.05 μM [5].
Niclosamide strongly inhibited the proliferation and colony formation of Du145 prostate cancer cells with IC50 values of 0.7 and 0.1 μM. Niclosamide dose dependently induced G0/G1 phase arrest and apoptosis of Du145 cancer cells [4]. Niclosamide inhibited cell viability of 3 Adrenocortical carcinoma (ACC) cell lines BD140A, SW-13, and NCI-H295R with IC50s of 0.12 μM, 0.15 μM, and 0.53 μM, respectively [6].
Niclosamide (ethanolamine salt) (1,500 ppm in HFD(high-fat diet)) significantly reduced fasting blood glucose concentrations in mice with HFD for 4 months [3]. Niclosamide (ethanolamine salt) is rapidly metabolized by the liver, with a half-life of about 1.5 h and no accumulation in the body after several hours [3].The LD50 of Niclosamide (ethanolamine salt) in rats is 10,000 mg kg-1 body weight [3].Oral niclosamide inhibited tumor growth and the progression of human ovarian cancer and colon cancer in xenograft animal models [7,8].
References:
[1]. Frayha G J, Smyth J D, Gobert J G, et al. The mechanisms of action of antiprotozoal and anthelmintic drugs in man[J]. General Pharmacology: The Vascular System, 1997, 28(2): 273-299.
[2]. Sheth U K. Mechanisms of anthelmintic action[J]. Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrès des recherches pharmaceutiques, 1975: 147-157.
[3]. Tao H, Zhang Y, Zeng X, et al. Niclosamide ethanolamine–induced mild mitochondrial uncoupling improves diabetic symptoms in mice[J]. Nature medicine, 2014, 20(11): 1263-1269.
[4]. Ren X, Duan L, He Q, et al. Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway[J]. ACS medicinal chemistry letters, 2010, 1(9): 454-459..
[5]. Chen M, Wang J, Lu J, et al. The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling[J]. Biochemistry, 2009, 48(43): 10267-10274.
[6]. Satoh K, Zhang L, Zhang Y, et al. Identification of Niclosamide as a Novel Anticancer Agent for Adrenocortical CarcinomaNiclosamide in Adrenal Cancer[J]. Clinical Cancer Research, 2016, 22(14): 3458-3466.
[7]. King M L, Lindberg M E, Stodden G R, et al. WNT7A/β-catenin signaling induces FGF1 and influences sensitivity to niclosamide in ovarian cancer[J]. Oncogene, 2015, 34(26): 3452-3462.
[8]. Osada T, Chen M, Yang X Y, et al. Antihelminth Compound Niclosamide Downregulates Wnt Signaling and Elicits Antitumor Responses in Tumors with Activating APC MutationsNiclosamide Inhibits Wnt Signaling and Colorectal Cancer Growth[J]. Cancer research, 2011, 71(12): 4172-4182.
氯硝柳胺是一种经美国食品和药物管理局 (FDA) 批准用于治疗肠道蛔虫感染的驱虫药[1,2]。该药物的作用机制是解偶联寄生虫[1,2]的线粒体,具有极好的安全性。氯硝柳胺（乙醇胺盐）是氯硝柳胺的一种盐形式,具有较高的水溶性[1-3]。
氯硝柳胺剂量依赖性地抑制 STAT3 依赖性荧光素酶报告基因活性,IC50 为 0.25 ± 0.07 μM [4]。氯硝柳胺抑制由完全激动剂 (Wnt) 诱导的 Wnt/Frizzled 信号传导,IC50 为 0.5 ± 0.05 μM [5]。
Niclosamide 强烈抑制 Du145 前列腺癌细胞的增殖和集落形成,IC50 值为 0.7 和 0.1 μM。氯硝柳胺剂量依赖性诱导 Du145 癌细胞 G0/G1 期阻滞和凋亡[4]。氯硝柳胺抑制 3 种肾上腺皮质癌 (ACC) 细胞系 BD140A、SW-13 和 NCI-H295R 的细胞活力,IC50 分别为 0.12 μM、0.15 μM 和 0.53 μM [6]。\n
氯硝柳胺（乙醇胺盐）（在 HFD（高脂肪饮食）中为 1,500 ppm）在 4 个月内显着降低了 HFD 小鼠的空腹血糖浓度[3]。氯硝柳胺（乙醇胺盐）经肝脏快速代谢,半衰期约为1.5 h,数小时后体内无蓄积[3]。氯硝柳胺（乙醇胺盐）的LD50在体内大鼠为 10,000 mg kg-1 体重[3]。在异种移植动物模型中口服氯硝柳胺抑制肿瘤生长和人卵巢癌和结肠癌的进展[7,8].
| Cas No. | 1420-04-8 | SDF | |
| 别名 | 氯硝柳胺乙醇胺盐,BAY2353 olamine | ||
| Canonical SMILES | OC1=C(C(NC2=CC=C([N+]([O-])=O)C=C2Cl)=O)C=C(Cl)C=C1.NCCO | ||
| 分子式 | C13H8Cl2N2O4•C2H7NO | 分子量 | 388.2 |
| 溶解度 | DMF: 30 mg/mL,DMSO: 30 mg/mL,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/mL,Ethanol: 0.25 mg/mL | 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 | 2.576 mL | 12.88 mL | 25.7599 mL |
| 5 mM | 0.5152 mL | 2.576 mL | 5.152 mL |
| 10 mM | 0.2576 mL | 1.288 mL | 2.576 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。
Niclosamide ethanolamine salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway
Cells 2022 Jan 20;11(3):346.PMID:35159160DOI:10.3390/cells11030346.
Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-β1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.
Niclosamide ethanolamine inhibits artery constriction
Pharmacol Res 2017 Jan;115:78-86.PMID:27872020DOI:10.1016/j.phrs.2016.11.008.
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of Niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.
Niclosamide ethanolamine ameliorates diabetes-related muscle wasting by inhibiting autophagy
Skelet Muscle 2021 Jun 9;11(1):15.PMID:34107998DOI:10.1186/s13395-021-00272-7.
Background: Diabetes-related muscle wasting is one of the devastating complications of diabetes, which is associated with muscle autophagy due to insulin-mediated glucose starvation. However, treatment for diabetes-related muscle wasting is limited. Our previous study already found that Niclosamide ethanolamine salt has the therapeutic effects on insulin deficiency of type 1 diabetes mice and muscle wasting induced by doxorubicin. Therefore, we aim to investigate the therapeutic effects of Niclosamide ethanolamine salt on diabetes-induced muscle wasting and to explore whether the mechanism is associated with muscle autophagy. Methods: Type 1 diabetes mice were induced by intraperitoneal injection of streptozotocin, then were fed with regular diet supplemented with 10 g/kg Niclosamide ethanolamine salt. The whole experiment lasted for 8 weeks. At the end of the study, grip strength, weights of tibialis anterior, gastrocnemius, soleus, and extensor digitorum longus muscle were measured. Tibialis anterior muscles stained with PAS were used for evaluating the fiber cross sectional area. Immunofluorescence analysis of myosin heavy chain expression in extensor digitorum longus and soleus muscle was used for determining the composition of the muscle fiber type. Electronic microscopy was applied to observe the autophagy in the atrophied muscle. Serum insulin levels and fasting blood glucose were also measured. Tissues of gastrocnemius muscle were used for detecting the expression of the proteins related to autophagy. Results: In this study, we found that Niclosamide ethanolamine salt could ameliorate muscle atrophy in the type 1 diabetes mice as well, such as enhancing the declined grip strength, improving limb weight and increasing the numbers of glycolytic muscle fiber. Electron microscopy also confirmed that there did exist abundant autophagic vacuoles in the atrophied muscle of the type 1 diabetes mice. Specifically, Niclosamide ethanolamine salt could reduce the over expression of autophagy-related proteins, including p-AMPK (Thr172), FoxO3a, p-ULK1 (Ser555), LC3B II, and p-p38 in gastrocnemius muscle of the type 1 diabetes mice. Conclusion: Niclosamide ethanolamine salt could ameliorate muscle wasting. The mechanisms underlying might be associated with inhibition of muscle autophagy.
[Molluscicidal effects of different formulations of Niclosamide ethanolamine salt in marshlands]
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2018 Oct 29;30(5):540-543.PMID:30567027DOI:10.16250/j.32.1374.2018095.
Objective: To evaluate the molluscicidal effects of different formulations of Niclosamide ethanolamine salt in marshlands. Methods: The molluscicidal effects of spraying with 25% suspension concentrate of Niclosamide ethanolamine salt (25% SCN) and 50% wettable powder formulation of Niclosamide ethanolamine salt (50% WPN), and dusting with 4% Niclosamide ethanolamine salt dustable powder (4% DP) for controlling Oncomelania hupensis snails were investigated and compared in the fields, and the cost-effectiveness was analyzed. Results: The corrected mortalities and the reduced rates of density of snails were 54.37%, 91.70%, 92.76%, 79.50%, and 59.55%, 95.93%, 97.63%, 94.15%, respectively, on 3, 7, 15, 30 d after spaying with 25% SCN, those on 3, 7, 15, 30 d after dusting with 4% DP were 59.10%, 91.83%, 95.56%, 93.34% and 65.03%, 94.93%, 97.61%, 97.28%, respectively; and those on 3, 7, 15, 30 d after spraying with 50% WPN were 76.29%, 91.68%, 93.12%, 81.59% and 81.24%, 97.02%, 97.84%, 95.27%, respectively. The cost of spraying with 25% SCN was 0.21 Yuan/m2, that of dusting with 4% DP was 0.39 Yuan/m2, and that of spraying with 50% WPN was 0.23 Yuan/m2 for snail control in the marshland. The cost of reduced one percentage of the corrected mortalities and the density of snails in controlling snails by 25% SCN, 4% DP and 50% WPN on 15 d were 22.68, 40.63, 25.17 Yuan and 21.54, 39.78, 23.95 Yuan, respectively. Conclusions: The three different formulations of Niclosamide are reliable and effective for snail control in marshlands. There are some differences among the different molluscicides in start time, pharmacodynamic characteristics, spraying methods in the field, cost of snail control, and influencing factors. Therefore, we need reasonably select the suitable molluscicides according to the environmental characteristics and working condition.
[Molluscicidal effect of suspension concentrate of Niclosamide ethanolamine salt]
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2017 Jul 27;29(4):416-419.PMID:29508571DOI:10.16250/j.32.1374.2016269.
Objective To evaluate the molluscicidal effect of suspension concentrate of Niclosamide ethanolamine salt (SCNE) against Oncomelania hupensis snails in laboratory and field. Methods The experiment of SCNE against the snails by using the immersing and spraying methods was performed in laboratory and field, with control groups of wettable powder of Niclosamide ethanolamine salt (WPN). Results In the laboratory, LC50(s) of SCNE for 24, 48 h and 72 h by using the immersion method were 0.092 6, 0.062 9 mg/L and 0.054 9 mg/L, respectively. The mortality rates of snails for 24, 48 h and 72 h by using the immersion method were all 100% with the concentrations of 0.25 mg/L. The mortality rates of snails were all 100% while spraying SCNE for 3 d in the laboratory with the concentrations of 0.25 g/m2. In Jiangling County, except 0.5 g/m3 SCNE immersing the snails for 24 h, the mortality rates of snails by using SCNE with the immersing method were all 100%. While the concentration of SCNE was 0.5 g/m3 or above, the mortality rates were all 100% after the use of it with the immersion method for 2 d in Gong'an County. In Jiangling County, the mortality rates of snails by using SCNE 0.5 g/m3 for 1 d, 3 d, and 7 d with the spraying method were 87.5%, 92.82% and 97.40% respectively. While the concentration of SCNE was 0.5 g/m3, the mortality rates were 85.94%, 86.78% and 94.21% respectively after the use of it with the spraying method for 1 d, 3 d, 7 d in Gong'an County, and the molluscicidal effect of SCNE (1.0 g/m2) was higher than that of WPN. Conclusion SCNE has a high molluscicidal effect in the laboratory and field, and it is a novel and simple formulation of Niclosamide.