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].