Niclosamide (CAS 50-65-7)

Niclosamide is an inhibitor of the Stat3 signaling pathway. Niclosamide inhibits the activation, nuclear translocation and transactivation of Stat3. Niclosamide displays selectivity for Stat3 over Stat1, Stat5, JAK1, JAK2 and Src kinases. Niclosamide inhibits the transcription of Stat3 target genes and induces cell growth inhibition, apoptosis and cell cycle arrest of cancer cells with constitutively active Stat3. Niclosamide is also a FRAP inhibitor via reversible inhibition of mTORC1 signaling and stimulates autophagy in vitro. Niclosamide displays antineoplastic effects in acute myelogenous leukemia (AML) stem cells.In its role as an anthelmintic, niclosamide disrupts mitochondrial metabolism in parasitic worms and animal models. Additionally, it functions as a STAT3 inhibitor, with an impressive IC50 of 0.25 μM, effectively inhibiting STAT3 transcriptional activity. Furthermore, it stimulates autophagy by reversibly inhibiting the mTORC1 signaling pathway in cells expressing EGFP-LC3.2. When used at a concentration of 3 µM, it completely inhibits the phosphorylation of ribosomal S6 kinases (S6K). Moreover, at 1 µM, it induces mitochondrial uncoupling, leading to a reduction in cellular ATP concentrations and an increase in the ADP to ATP ratio in HepG2 cells. It activates AMP-activated protein kinase (AMPK) in NIH3T3 cells and significantly enhances lipid oxidation in HepG2 cells by a factor of 5. Niclosamide belongs to the class of benzanilides, aromatic compounds characterized by an anilide group in which the carboxamide group is substituted with a benzene ring.