Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 1, Issue 9, Pages 454-459Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ml100146z
Keywords
STAT3 signaling pathway; inhibitor; niclosamide; apoptosis; cell cycle arrest
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Funding
- Chinese Academy of Sciences (CAS) [KSCX2-YWR-27]
- National Natural Science Foundation [21072192, 90813033]
- National High Technology Research and Development Program [2010CB529706, 2009CB940904]
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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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