Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Targeting YAP-TEAD Interaction with Honokiol to Inhibit Melanoma Progression and Metastasis

  • Chaelin Lee (Department of Biotechnology and Bioscience, Sejong University) ;
  • Hien Thi Thu Do (Department of Biotechnology and Bioscience, Sejong University) ;
  • Xiang Fei (College of Pharmacy, Gachon University) ;
  • Sanha Lee (College of Pharmacy, Gachon University) ;
  • Soonsil Hyun (College of Pharmacy, Chungbuk National University) ;
  • Seung-Yong Seo (College of Pharmacy, Gachon University) ;
  • Inmoo Rhee (Department of Biotechnology and Bioscience, Sejong University)
  • Received : 2025.11.01
  • Accepted : 2025.12.05
  • Published : 2026.01.01
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Abstract

The Hippo-YAP/TEAD pathway plays a central role in melanoma progression by regulating tumor cell proliferation, survival, and migration. Using a NanoLuc Binary Technology (NanoBiT) protein-protein interaction assay, we screened honokiol-based small molecules and identified several analogues that disrupt the YAP-TEAD interaction. HK03 was the most effective analogue, leading to a pronounced reduction in Cyr61 levels and diminished Erk and Akt phosphorylation in B16-F10 melanoma cells. HK03 also blocked epithelial-mesenchymal transition (EMT) and impaired melanoma cell migration in wound-healing assays. In vivo, HK03 treatment markedly reduced metastatic burden in a B16-F10 lung metastasis model. These findings suggest that honokiol derivatives, particularly HK03, represent potential lead compounds for targeting the YAP-TEAD axis in melanoma therapy.

Keywords

Acknowledgement

This research was supported by Basic Science Research program through National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. NRF-2021R1F1A1063321 for I.R.), and by the National Research Foundation of Korea (NRF-2020R1A6A1A03043708 and NRF-2022R1A2C1092715 for S.S.), as well as the Regional Innovation System & Education (RISE) program through the (Chungbuk Regional Innovation System & Education Center), funded by the Ministry of Education (MOE) and the (Chungcheongbuk-do), Republic of Korea (2025-RISE-11-014-03 for S.H.).

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