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

被引：29
|
作者：
Kawamura, Tatsuro [1 ]
Matsubara, Kohei [1 ]
Otaka, Hitomi [1 ]
Tashiro, Etsu [1 ]
Shindo, Kazutoshi [2 ]
Yanagita, Ryo C. [3 ]
Irie, Kazuhiro [3 ]
Imoto, Masaya [1 ]
机构：
[1] Keio Univ, Fac Sci & Technol, Dept Biosci & Informat, Kohoku Ku, Yokohama, Kanagawa 2238522, Japan
[2] Japan Womens Univ, Dept Food & Nutr, Bunkyo Ku, Tokyo 1128681, Japan
[3] Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Kyoto 6068502, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 14期
关键词：
Chemical library; Natural product; Unnatural Natural Product; C38OX6; XIAP; Cancer; PHORBOL ESTER BINDING; CONFORMATIONALLY RESTRICTED ANALOGS; KINASE-C ISOZYMES; DRUG DISCOVERY; TELEOCIDIN-B; PROTEIN; ELUCIDATION; APOPTOSIS; (-)-INDOLACTAM-V; TRANSLOCATION;
D O I：
10.1016/j.bmc.2011.05.009
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4377 / 4385
页数：9
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