Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus

Yasushi Takemoto, Hidenori Watanabe, Kenji Uchida, Koji Matsumura, Koichi Nakae, Etsu Tashiro, Kazutoshi Shindo, Takeshi Kitahara, Masaya Imoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


Cancer cell migration is a required step in cancer metastasis. We screened for inhibitors of cancer cell migration of microbial origin, and obtained moverastin, a member of the cylindrol family, from Aspergillus sp. F7720. However, the results of an NMR spectroscopic analysis raised the possibility that moverastin is a mixture of two diastereomers. Separation of the C-10 epimers of synthetic moverastin and a bioassay revealed that both diastereomers (moverastins A and B) had inhibitory effects on cell migration. Furthermore, we demonstrated that moverastins A and B inhibited FTase in vitro, and they also inhibited both the membrane localization of H-Ras and the activation of the PI3K/Akt pathway in EC17 cells. Thus, moverastins inhibited the migration of tumor cells by inhibiting the farnesylation of H-Ras, and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.

Original languageEnglish
Pages (from-to)1337-1347
Number of pages11
JournalChemistry and Biology
Issue number12
Publication statusPublished - 2005 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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