@article{20c254da968f4cdf9e849725205a3d55,
title = "Establishment of live-cell-based coupled assay system for identification of compounds to modulate metabolic activities of cells",
abstract = "In this study, we present a live-cell-based fluorometric coupled assay system to identify the compounds that can regulate the targeted metabolic pathways in live cells. The assay is established through targeting specific metabolic pathways and using “input” and “output” metabolite pairs. The changes in the extracellular output that are generated and released into the extracellular media from the input are assessed as the activity of the pathway. The screening for the glycolytic pathway and amino acid metabolism reveals the activities of the present drugs, 6-BIO and regorafenib, that regulate the metabolic fate of tumor cells.",
keywords = "chemical biology, coupled assays, fluorescent probes, glucolysis, glutaminolysis, metabolism",
author = "Kouichi Yanagi and Toru Komatsu and Shusuke Ogihara and Takayoshi Okabe and Hirotatsu Kojima and Tetsuo Nagano and Tasuku Ueno and Kenjiro Hanaoka and Yasuteru Urano",
note = "Funding Information: This work was financially supported by MEXT (24655147, 15H05371, 15K14937, 17K19477, 18H04538, 19H02846, and 20H04694 to T.K), JST (PRESTO, PRESTO Network, CREST, and START to T.K.), and ImPACT and AMED (to Y.U.). T.K. was supported by The Naito Foundation, The Mochida Memorial Foundation for Medical and Pharmaceutical Research, and The Tokyo Biochemical Research Foundation. The inhibitor screening project was supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from AMED (JP19am0101086, support no. 2032). K.Y. and S.O. are recipients of the JSPS Young Scientist Fellowship. The project was also supported by the JSPS Core-to-Core program (JPJSCCA20170007). The global metabolite analysis was performed as a contract service by Human Metabolome Technologies. English proofreading was performed by Editage. T.K. conceived the experimental design. K.Y. synthesized and characterized the compounds. K.Y. and S.O. performed the chemical and biological experiments. H.K. T.O. and T.N. organized the compound library and supervised the screening experiments. The experimental data were analyzed under the supervision of T.K. K.H. T.U. and Y.U. The manuscript was written by K.Y. and T.K. The authors declare no competing interests. Funding Information: This work was financially supported by MEXT ( 24655147 , 15H05371 , 15K14937 , 17K19477 , 18H04538 , 19H02846 , and 20H04694 to T.K), JST ( PRESTO , PRESTO Network , CREST , and START to T.K.), and ImPACT and AMED (to Y.U.). T.K. was supported by The Naito Foundation , The Mochida Memorial Foundation for Medical and Pharmaceutical Research , and The Tokyo Biochemical Research Foundation . The inhibitor screening project was supported by the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from AMED ( JP19am0101086 , support no. 2032). K.Y. and S.O. are recipients of the JSPS Young Scientist Fellowship . The project was also supported by the JSPS Core-to-Core program ( JPJSCCA20170007 ). The global metabolite analysis was performed as a contract service by Human Metabolome Technologies. English proofreading was performed by Editage. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = jul,
day = "6",
doi = "10.1016/j.celrep.2021.109311",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}