SAR study of a novel triene-ansamycin group compound, quinotrierixin, and related compounds, as inhibitors of ER stress-induced XBP1 activation I. Taxonomy, fermentation, isolation, biological activities and SAR study

Tatsuro Kawamura, Etsu Tashiro, Kohta Yamamoto, Kazutoshi Shindo, Masaya Imoto

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In the course of screening for an inhibitor of ER stress-induced XBP1 activation, we isolated a new member of the triene-ansamycin group compound, quinotrierixin, from a culture broth of Streptomyces sp. PAE37. Quinotrierixin inhibited thapsigargin-induced XBP1 activation in HeLa cells with an IC 50 of 0.067 μM. We found that other triene-ansamycin group compounds such as demethyltrienomycin A and mycotrienin I also inhibited ER stress-induced XBP1 activation. Moreover, we performed SAR study of twelve triene-ansamycin group compounds. The study showed that OH group at C-13 was crucial, and CH3 group at C-14 would be important for the XBP1 inhibitory activity.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalJournal of Antibiotics
Volume61
Issue number5
DOIs
Publication statusPublished - 2008 May 1

Keywords

  • ER stress
  • Triene-ansamycin
  • XBP1

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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