Niclosamide

Background:

Antihelminthic, molluscicide and trypanocidal agent that inhibits mitochondrial oxidative phosphorylation and anaerobic ATP production. Anticancer agent with antiproliferative activity in a broad spectrum of cancer cells. Targets and inhibits multiple signaling pathways, including STAT3, NF-kB, Wnt/β-catenin, Notch and mTORC1. Shown to block TNF-α-induced IκBα phosphorylation, translocation of p65 and the expression of NF-κB-regulated genes and elevates reactive oxygen species (ROS) levels. Promotes Frizzled1 internalization, down-regulates the expression of Dishevelled-2 protein and inhibits β-catenin stabilization. Inhibits mTORC1 but not mTORC2 signaling in cells maintained in nutrient-rich conditions. Cell permeable selective STAT3 inhibitor (IC50=0.25μM). Inhibits the activation, nuclear translocation and transactivation of STAT3. Selective over STAT1, STAT5, JAK1, JAK2 and Src kinases. Induces cell cycle arrest, growth inhibition, autophagy and apoptosis. Inhibits S100A4 (Metastasin-1)-induced metastasis in vivo. Inhibits androgen receptor (AR) splice variants. Anti-inflammatory compound. Quorum sensing inhibitor. Broad-spectrum antiviral agent that targets acidified endosomes. Has been shown to inhibit replication of SARS and is a potential candidate to treat SARS-CoV-2 (COVID-19) infections. Antiobesity and antidiabetic agent. Positive allosteric neuropetide Y4 receptor ligand and increases energy expenditure and lipid metabolism through mitochondrial uncoupling.