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Identification of Niclosamide as a New Small-Molecule Inhibitor of the STAT3 Signaling Pathway

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† Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, #190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou, China 510530
‡ Zhongshan Medical School, Sun Yat-Sen University, #74 Second Zhongshan Road, Guangzhou, China 510080
*To whom correspondence should be addressed. Tel: 86-20-32015276. Fax: 86-20-32015299. E-mail: [email protected]
Cite this: ACS Med. Chem. Lett. 2010, 1, 9, 454–459
Publication Date (Web):September 7, 2010
https://doi.org/10.1021/ml100146z
Copyright © 2010 American Chemical Society
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    Abstract

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    Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers with constitutively active STAT3. In this study, we report the identification of niclosamide, an FDA-approved anthelmintic drug, as a new small-molecule inhibitor of the STAT3 signaling pathway. This compound potently inhibited the activation and transcriptional function of STAT3 and consequently induced cell growth inhibition, apoptosis, and cell cycle arrest of cancer cells with constitutively active STAT3. Our study provides a new promising lead compound with a salicylic amide scaffold for the development of STAT3 pathway inhibitors as novel molecularly targeted anticancer drugs.

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    Typical experimental procedures for the luciferase reporter assay, Western blotting, immunofluorescence assay, cell proliferation inhibition assay, flow cytometric analysis, nuclear protein extraction, EMSA, and the kinase panel profiling results. This material is available free of charge via the Internet at http://pubs.acs.org.

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