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

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.
Hyun Su Kim 1,  Taewoo Kim 1,  Hyejin Ko 1,  Jeeyeon Lee 1,  Yeong Shik Kim 1,  Young-Ger Suh 2
Affiliations

Affiliations

  • 1 College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
  • 2 College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; College of Pharmacy, CHA University, 120 Haeryong-ro, Pochen-si, Gyeonggi-do 11160, Republic of Korea. Electronic address: ygsuh@cha.ac.kr.
PMID: 28705432 DOI: 10.1016/j.bmc.2017.06.036
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.

Keywords

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

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