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

doi:10.1016/j.bmc.2011.05.009

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

生命情報学科

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
巻	19
号	14
DOI	https://doi.org/10.1016/j.bmc.2011.05.009
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

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

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10.1016/j.bmc.2011.05.009

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title = "Generation of 'Unnatural Natural Product' library and identification of a small molecule inhibitor of XIAP",

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.",

keywords = "C38OX6, Cancer, Chemical library, Natural product, Unnatural Natural Product, XIAP",

author = "Tatsuro Kawamura and Kohei Matsubara and Hitomi Otaka and Etsu Tashiro and Kazutoshi Shindo and Yanagita, {Ryo C.} and Kazuhiro Irie and Masaya Imoto",

note = "Funding Information: We are grateful to T. Watabe, Y. Fujimoto, and Y. Matsui (Keio University) for help with construction of the UNP library. This study was supported in part by a 2009 Innovative Research Program Award from the Japanese Society of Bioscience, Biotechnology, and Agrochemistry (JSBBA). T.K. was a research assistant for the Global COE Program for Human Metabolomic Systems Biology. ",

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AU - Kawamura, Tatsuro

AU - Matsubara, Kohei

AU - Otaka, Hitomi

AU - Tashiro, Etsu

AU - Shindo, Kazutoshi

AU - Yanagita, Ryo C.

AU - Irie, Kazuhiro

AU - Imoto, Masaya

N1 - Funding Information: We are grateful to T. Watabe, Y. Fujimoto, and Y. Matsui (Keio University) for help with construction of the UNP library. This study was supported in part by a 2009 Innovative Research Program Award from the Japanese Society of Bioscience, Biotechnology, and Agrochemistry (JSBBA). T.K. was a research assistant for the Global COE Program for Human Metabolomic Systems Biology.

PY - 2011/7/15

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KW - C38OX6

KW - Cancer

KW - Chemical library

KW - Natural product

KW - Unnatural Natural Product

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

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ASJC Scopus subject areas

UN SDG

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