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

Bioorg Med Chem. 2017 Oct 1;25(19):5032-5040. doi: 10.1016/j.bmc.2017.06.036. Epub 2017 Jun 23.


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.

Keywords: (−)-Galiellalactone; MDA-MB-468; STAT3; TNBC; [3.3] bicyclic lactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Antineoplastic Agents
  • Lactones
  • STAT3 Transcription Factor
  • galiellalactone