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Development of a highly-specific 18F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping
https://repo.qst.go.jp/records/82744
https://repo.qst.go.jp/records/82744645ee1f7-fdf0-4fea-be4f-50a01abaeffb
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-12-17 | |||||
| タイトル | ||||||
| タイトル | Development of a highly-specific 18F-labeled irreversible positron emission tomography tracer for monoacylglycerol lipase mapping | |||||
| 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 |
Chen, Zhen
× Chen, Zhen× Mori, Wakana× Rong, Jian× A. Schafroth, Michael× Shao, Tuo× S. Van, Richard× Ogasawara, Daisuke× Yamasaki, Tomoteru× Hiraishi, Atsuto× Hatori, Akiko× Chen, Jiahui× Zhang, Yiding× Kuan, Hu× Fujinaga, Masayuki× Sun, Jiyun× Yu, Qingzhen× L. Collier, Thomas× Shao, Yihan× F. Cravatt, Benjamin× Josephson, Lee× Ming-Rong, Zhang× Liang, Huan× Wakana, Mori× Tomoteru, Yamasaki× Atsuto, Hiraishi× Akiko, Hatori× Zhang, Yiding× Kuan, Hu× Masayuki, Fujinaga× Zhang, Ming-Rong× Liang, Huan |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abstract Monoacylglycerol lipase (MAGL) is a serine hydrolase, which metabolizes 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) in the central nervous system (CNS). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified 14 as a lead compound, which was then radiolabeled with fluorine-18 via a facile SNAr reaction to form 2-[18F]fluoropyridinyl scaffold. Excellent blood−brain barrier penetration and high in vivo binding specificity was validated for radioligand [18F]14 (also named as [18F]MAGL-1902). This work may serve as a roadmap for clinical translation and further design of potent 18F-labeled MAGL PET tracers. KEY WORDS Monoacylglycerol lipase (MAGL); Central nervous system (CNS); 2-Arachidonylglycerol (2-AG); Arachidonic acid (AA); Positron emission tomography (PET); Fluorine-18 |
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| 書誌情報 |
Acta Pharmaceutica Sinica B 巻 11, 号 6, p. 1686-1695, 発行日 2020-12 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2211-3835 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.apsb2021.01.021 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/pii/S2211383521000381?via%3Dihub | |||||
