Kinase (STAT3) signaling inhibitor; Autophagy modulator. Regulates mTORC1 pathway, whose members interact with SARS-CoV-2 N and Orf8 proteins; reduces replication of related coronavirus MERS-CoV via SKP2 inhibition. Gassen et al. Nat. Commun, 10:5770 2019, https://doi.org/10.1038/s41467-019-13659-4; Gassen et al. bioRxiv, Apr 15 2020, https://doi.org/10.1101/2020.04.15.997254; Laise et al. bioRxiv, May 17 2020, https://doi.org/10.1101/2020.05.12.091256; Xu et al. ACS Infect. Dis., Mar 3 2020, https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00052.
Biochemicals & reagents
1) Balgi et al. (2009), Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling; PloS One, 4 e7124 2) Ren et al. (2010), Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway; ACS Med. Chem. Lett., 1 454
Niclosamide reversibly inhibits mTORC1 signaling and stimulates autophagy (1). This compound inhibits activation and nuclear translocation of STAT3 selectively over STAT1 and STAT5. It also inhibits transcription of STAT3 target genes and induces cell cycle arrest and apoptosis in cells with constitutively active STAT3 (2).