2. Academic Validation
  3. Identification of a derivative of the alkaloid emetine as an inhibitor of the YAP-TEAD interaction and its potential as an anticancer agent

Identification of a derivative of the alkaloid emetine as an inhibitor of the YAP-TEAD interaction and its potential as an anticancer agent

  • Biosci Biotechnol Biochem. 2023 Feb 21;zbad022. doi: 10.1093/bbb/zbad022.
Saaya Sekine 1 2,  Shohei Takase 1,  Runa Hayase 1,  Kota Noritsugu 1,  Yuki Maemoto 1,  Yasue Ichikawa 3,  Kenji Ogawa 3 4,  Yasumitsu Kondoh 5,  Hiroyuki Osada 5 6,  Minoru Yoshida 2 3 7,  Akihiro Ito 1 2
Affiliations

Affiliations

  • 1 Laboratory of Cell Signaling, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences; Hachioji, Tokyo, Japan.
  • 2 Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science; Wako, Saitama, Japan.
  • 3 Drug Discovery Seed Compounds Exploratory Unit, RIKEN Center for Sustainable Resource Science; Wako, Saitama, Japan.
  • 4 Laboratory of Veterinary Epizootiology, College of Bioresource Sciences, Nihon University; Fujisawa, Kanagawa, Japan.
  • 5 Chemical Resource Development Research Unit, RIKEN Center for Sustainable Resource Science; Wako, Saitama, Japan.
  • 6 Department of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
  • 7 Department of Biotechnology, the University of Tokyo; Bunkyo-ku, Tokyo, Japan.
PMID: 36809780 DOI: 10.1093/bbb/zbad022
Abstract

TEAD is a transcription factor responsible for the output of the tumor suppressor Hippo pathway. The transcriptional activity of TEAD requires molecular interaction with its transcriptional coactivator YAP. Aberrant activation of TEAD is deeply involved in tumorigenesis and is associated with poor prognosis, suggesting that inhibitors targeting the YAP-TEAD system are promising as antitumor agents. In this study, we identified NPD689, an analog of the natural product alkaloid emetine, as an inhibitor of the YAP-TEAD interaction. NPD689 suppressed the transcriptional activity of TEAD and reduced the viability of human malignant pleural mesothelioma and non-small cell lung Cancer cells but not the viability of normal human mesothelial cells. Our results suggest that NPD689 is not only a new useful chemical tool for elucidating the biological role of the YAP-TEAD system but also has potential as a starting compound for developing a Cancer therapeutic agent that targets the YAP-TEAD interaction.

Keywords

Anticancer agent; Emetine; Hippo pathway; TEAD; YAP.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-138565
    99.27%, YAP1/TAZ-TEAD Inhibitor
    YAP