Identification of galiellalactone-based novel STAT3-selective inhibitors with cytotoxic activities against triple-negative breast cancer cell lines.

Abstract

Signal transducer and activator of transcription 3 (STAT3) is phosphorylated in breast cancer cells, particularly triple-negative breast cancers (TNBCs). Therefore, the inhibition of constitutive phosphorylated STAT3 is a promising therapeutic for TNBC treatment. Recently, a series of novel STAT3 inhibitors based on natural (-)-galiellalactone have been identified to inhibit STAT3 phosphorylation at the Tyr705 residue. Interestingly, the truncation of the cyclohexene moiety of (-)-galiellalactone to [3.3] bicyclic lactone as a pharmacophoric core produced improved cytotoxic effects against TNBCs. The potent analogues 16 and 17, identified from a STAT3-mediated luciferase reporter assay, selectively inhibited the STAT3 signaling pathway without affecting STAT1 or STAT5.

• Authors: Hyun Su Kim, Taewoo Kim, Hyejin Ko, Jeeyeon Lee, Yeong Shik Kim, Young-Ger Suh
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 25 Issue 19 Pg. 5032-5040 (10 01 2017) ISSN: 1464-3391 [Electronic] England
• PMID: 28705432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Lactones
• STAT3 Transcription Factor
• galiellalactone

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Breast (drug effects, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Female
• Humans
• Lactones (chemistry, pharmacology)
• Phosphorylation (drug effects)
• STAT3 Transcription Factor (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)