Unveiling poliumoside: A herbal-derived FAK kinase inhibitor with anti-proliferative and anti-metastatic efficacy

  • Phytomedicine. 2025 Dec 30:150:157747. doi: 10.1016/j.phymed.2025.157747.
Huiling Zhang  1 ,  Yuna Shao  1 ,  Di Lu  1 ,  Chenkang Ma  1 ,  Liying Zhang  1 ,  Yang Yang  2 ,  Jianjun Li  2 ,  Yuanyuan Zeng  2 ,  Jianjie Zhu  2 ,  Jian-An Huang  2 ,  Zhe Lei  3 ,  Zeyi Liu  4
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
  • 2. Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China; Suzhou Key Laboratory for Respiratory Diseases, Suzhou, 215006, China.
  • 3. Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China. Electronic address: [email protected].
  • 4. Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China; Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China; Suzhou Key Laboratory for Respiratory Diseases, Suzhou, 215006, China; Cancer Institute, Suzhou Medical College, Soochow University, Suzhou, 215123, China. Electronic address: [email protected].
PMID: 41485292 DOI: 10.1016/j.phymed.2025.157747
Abstract

Focal adhesion kinase (FAK) is an attractive therapeutic target overexpressed in numerous cancers. Despite extensive efforts, no FAK Inhibitor has reached the market. Here, we identified poliumoside (Pol), a compound from Chinese herbs, as a novel FAK Inhibitor through high-throughput virtual screening. Pol exhibited potent anti-proliferative and anti-metastatic activities both in vitro and in vivo. Mechanistically, Pol directly binds to His89 of FAK, thereby inhibiting its autophosphorylation at Y397. This inhibition led to the downregulation of the ERK-c-Myc axis, reduced transcription of IL-6, and consequent suppression of the JAK3-STAT3 signaling pathway. Our findings establish Pol as a promising FAK-targeting agent, exerting its anti-tumor effects in a FAK-dependent manner.

Keywords
ERK; FAK; IL-6; NSCLC; STAT3; poliumoside.
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