Niclosamide, an anthelmintic drug, is the small-molecule inhibitor of STAT3 with an IC50 value of 0.25±0.07μM[1]. Niclosamide has been widely used in cancer research and metabolic regulation studies, and is employed as a model compound to develop a series of derivatives[2].
In vitro, Niclosamide treatment for 3 days significantly inhibited the viability of HL-60 cells, with an IC50 value of 0.28 ± 0.03μM[3]. Treatment with 0.6µM Niclosamide for 24 hours significantly inhibited the expression of LRP6 in HEK293 cells and blocked the activation of the Wnt/β-catenin signaling pathway[4]. Treatment with 20μM Niclosamide for 24 hours significantly inhibited the viability of TPC-1 cells, causing the cells to become vacuolated and disintegrated[5]. Treatment with 0.5μM Niclosamide for 12 hours significantly inhibited the migration rate of BD140A cells and reduced the levels of epithelial-mesenchymal transition mediators (N-cadherin and vimentin)[6].
In vivo, Niclosamide treatment via daily intraperitoneal injection at a dose of 10mg/kg for 21 days can significantly alleviate the pulmonary fibrosis symptoms induced by bleomycin in mice and inhibit the accumulation of collagen[7]. Oral administration of Niclosamide at a dose of 200mg/kg/day for 9 weeks improved myocardial hypertrophy, cardiac fibrosis and cardiac dysfunction in mice with aortic coarctation [8].
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.
[2] Kang B, Mottamal M, Zhong Q, et al. Design, synthesis, and evaluation of niclosamide analogs as therapeutic agents for enzalutamide-resistant prostate cancer[J]. Pharmaceuticals, 2023, 16(5): 735.
[3] Chae H D, Cox N, Dahl G V, et al. Niclosamide suppresses acute myeloid leukemia cell proliferation through inhibition of CREB-dependent signaling pathways[J]. Oncotarget, 2017, 9(4): 4301.
[4] Lu W, Lin C, Roberts M J, et al. Niclosamide suppresses cancer cell growth by inducing Wnt co-receptor LRP6 degradation and inhibiting the Wnt/β-catenin pathway[J]. PloS one, 2011, 6(12): e29290.
[5] Yu K, Wang T, Li Y, et al. Niclosamide induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in human thyroid cancer in vitro[J]. Biomedicine & Pharmacotherapy, 2017, 92: 403-411.
[6] Satoh K, Zhang L, Zhang Y, et al. Identification of niclosamide as a novel anticancer agent for adrenocortical carcinoma[J]. Clinical Cancer Research, 2016, 22(14): 3458-3466.
[7] Boyapally R, Pulivendala G, Bale S, et al. Niclosamide alleviates pulmonary fibrosis in vitro and in vivo by attenuation of epithelial-to-mesenchymal transition, matrix proteins & Wnt/β-catenin signaling: A drug repurposing study[J]. Life sciences, 2019, 220: 8-20.
[8] Fu Y, Hu N, Cao M, et al. Anthelmintic niclosamide attenuates pressure-overload induced heart failure in mice[J]. European Journal of Pharmacology, 2021, 912: 174614.
Niclosamide是一种驱虫药，是STAT3的小分子抑制剂，IC50值为0.25±0.07μM[1]。该药物广泛应用于癌症研究和代谢调控研究，并作为先导化合物用于开发系列衍生物[2]。
在体外，Niclosamide处理3天可显著抑制HL-60细胞活力，IC50值为0.28±0.03μM[3]。0.6µM的Niclosamide处理HEK293细胞24小时能显著抑制LRP6表达并阻断Wnt/β-catenin信号通路激活[4]。20μM的Niclosamide处理TPC-1细胞24小时可显著抑制细胞活力，导致细胞空泡化并解体[5]。0.5μM的Niclosamide处理BD140A细胞12小时能显著抑制细胞迁移率，降低上皮-间质转化介质（N-钙黏蛋白和波形蛋白）水平[6]。
在体内，小鼠每日腹腔注射Niclosamide（10mg/kg；持续21天）可显著缓解博来霉素诱导的肺纤维化症状并抑制胶原沉积[7]。主动脉缩窄小鼠每日口服200mg/kg剂量的Niclosamide（持续9周）能改善心肌肥大、心脏纤维化和心功能障碍[8]。