Generation of 'Unnatural Natural Product' library and identification of a small molecule inhibitor of XIAP

Tatsuro Kawamura, Kohei Matsubara, Hitomi Otaka, Etsu Tashiro, Kazutoshi Shindo, Ryo C. Yanagita, Kazuhiro Irie, Masaya Imoto

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Natural products have been utilized for drug discovery. To increase the source diversity, we generated a new chemical library consisting of chemically modified microbial metabolites termed 'Unnatural Natural Products' by chemical conversion of microbial metabolites in crude broth extracts followed by purification of reaction products with the LC-photo diode array-MS system. Using this library, we discovered an XIAP inhibitor, C38OX6, which restored XIAP-suppressed enzymatic activity of caspase-3 in vitro. Furthermore, C38OX6 sensitized cancer cells to anticancer drugs, whereas the unconverted natural product did not. These findings suggest that our library could be a useful source for drug seeds.

Original languageEnglish
Pages (from-to)4377-4385
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number14
DOIs
Publication statusPublished - 2011 Jul 15

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Keywords

  • C38OX6
  • Cancer
  • Chemical library
  • Natural product
  • Unnatural Natural Product
  • XIAP

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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