Structure Optimization of Gatastatin for the Development of γ-Tubulin-Specific Inhibitor

Kana Shintani, Haruna Ebisu, Minagi Mukaiyama, Taisei Hatanaka, Takumi Chinen, Daisuke Takao, Yoko Nagumo, Akira Sakakura, Ichiro Hayakawa, Takeo Usui, Takeo Usui

Research output: Contribution to journalArticle


Gatastatin (O7-benzyl glaziovianin A) is a γ-tubulin-specific inhibitor that is used to investigate γ-tubulin function in cells. We have previously reported that the unsubstituted phenyl ring of the O7-benzyl group in gatastatin is important for γ-tubulin inhibition. To obtain further structural information regarding γ-tubulin inhibition, we synthesized several gatastatin derivatives containing a fixed O7-benzyl moiety. Modifications of the B-ring resulted in drastic decrease in cytotoxicity, abnormal spindle formation activity, and inhibition of microtubule (MT) nucleation. In contrast, various O6-alkylated gatastatin derivatives showed potent cytotoxicity, induced abnormal spindle formation, and inhibited MT nucleation. We had previously reported that O6-benzyl glaziovianin A is a potent α/β-tubulin inhibitor; thus, these new results suggest that the O6-position restricts affinity for α/β- and γ-tubulin. Considering that an O7-benzyl group increases specificity for γ-tubulin, more potent and specific γ-tubulin inhibitors can be generated through O6-modifications of gatastatin.

Original languageEnglish
Pages (from-to)1125-1129
Number of pages5
JournalACS Medicinal Chemistry Letters
Issue number6
Publication statusPublished - Jun 11 2020


  • microtubule nucleation
  • spindle
  • structure-activity relationships
  • γ-Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Shintani, K., Ebisu, H., Mukaiyama, M., Hatanaka, T., Chinen, T., Takao, D., Nagumo, Y., Sakakura, A., Hayakawa, I., Usui, T., & Usui, T. (2020). Structure Optimization of Gatastatin for the Development of γ-Tubulin-Specific Inhibitor. ACS Medicinal Chemistry Letters, 11(6), 1125-1129.