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In vitro and in vivo evaluation of 11C-labeled azetidine-carboxylates for imaging monoacylglycerol lipase by PET imaging studies
https://repo.qst.go.jp/records/48787
https://repo.qst.go.jp/records/487876104f534-2248-495e-b87c-6c029a237db2
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-03-01 | |||||
| タイトル | ||||||
| タイトル | In vitro and in vivo evaluation of 11C-labeled azetidine-carboxylates for imaging monoacylglycerol lipase by PET imaging studies | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Cheng, Ran
× Cheng, Ran× Mori, Wakana× Ma, Longle× Alhouayek, Mireille× Hatori, Akiko× Zhang, Yiding× Ogasawara, Daisuke× Yuan, Gengyang× Chen, Zhen× Zhang, Xiaofei× Shi, Hang× Yamasaki, Tomoteru× Xie, Lin× Kumata, Katsushi× Fujinaga, Masayuki× Nagai, Yuji× Minamimoto, Takafumi× Svensson, Mona× Lu, Wang× Du, Yunfei× Jo Ondrechen, Mary× Vasdev, Neil× F Cravatt, Benjamin× Fowler, Christopher× Ming-Rong, Zhang× H Liang, Steven× Mori, Wakana× Hatori, Akiko× Zhang, Yiding× Yamasaki, Tomoteru× Xie, Lin× Kumata, Katsushi× Fujinaga, Masayuki× Nagai, Yuji× Minamimoto, Takafumi× Lu, Wang× Ming-Rong, Zhang× Liang, Huan |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing the endogenous cannabinoid ligand, 2-arachidonylglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including 11C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [11C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold. | |||||
| 書誌情報 |
Journal of Medicinal Chemistry 巻 61, p. 2278-2291, 発行日 2018-02 |
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| 出版者 | ||||||
| 出版者 | ACS Publications | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acs.jmedchem.7b01400 | |||||
