@article{418bbc3322f44305a757a1701576b87c,
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. ",
year = "2011",
month = jul,
day = "15",
doi = "10.1016/j.bmc.2011.05.009",
language = "English",
volume = "19",
pages = "4377--4385",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "14",
}