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

研究成果: Article査読

25 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)4377-4385
ページ数9
ジャーナルBioorganic and Medicinal Chemistry
19
14
DOI
出版ステータスPublished - 2011 7 15

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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