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Design, Synthesis, and Evaluation of 11C-Labeled 3-Acetylindole Derivatives as Novel Positron-Emission Tomography Imaging Agent for Diacylglycerol Kinase Gamma (DGKγ) in Brain
https://repo.qst.go.jp/records/85193
https://repo.qst.go.jp/records/851930bd25690-7c44-492c-af9f-003588715529
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-07-26 | |||||
| タイトル | ||||||
| タイトル | Design, Synthesis, and Evaluation of 11C-Labeled 3-Acetylindole Derivatives as Novel Positron-Emission Tomography Imaging Agent for Diacylglycerol Kinase Gamma (DGKγ) in Brain | |||||
| 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 |
Hattori, Yasushi
× Hattori, Yasushi× Tomoteru, Yamasaki× Ohashi, Tomohiro× Miyanohana, Yuhei× Kusumoto, Tomokazu× Maeda, Ryouta× Miyamoto, Maki× Debori, Yasuyuki× Hata, Akito× Zhang, Yiding× Hidekatsu, Wakizaka× Takeshi, Wakabayashi× Masayuki, Fujinaga× Yamashita, Ryo× Zhang, Ming-Rong× Koike, Tatsuki× Hattori, Yasushi× Tomoteru, Yamasaki× Zhang, Yiding× Hidekatsu, Wakizaka× Takeshi, Wakabayashi× Masayuki, Fujinaga× Zhang, Ming-Rong |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Diacylglycerol kinase gamma (DGKγ) is a subtype of DGK enzyme which catalyzes ATPdependent conversion of diacylglycerol to phosphatidic acid. DGKγ, localized in brain, plays some important role in central nervous system. However, its function has not been widely investigated. Positron emission tomography (PET) imaging of DGKγ validates target engagement of therapeutic DGKγ inhibitors and investigates DGKγ levels under normal and disease conditions. In this study, we designed and synthesized a series of 3-acetyl indole derivatives as candidates for PET imaging agents for DGKγ. Among the synthesized compounds, 2-((3-acetyl-1-(6-methoxypyridin-3-yl)-2-methyl-1H-indol-5-yl)oxy)-N-methylacetamide (9) exhibited potent inhibitory activity (IC50 = 30 nM) against DGKγ and desirable physicochemical properties allowing efficient blood-brain barrier penetration and low levels of undesirable nonspecific binding. The radio-labeling of 9 followed by PET imaging of wild-type and DGKγ- deficient mice and rats indicated that [11C]9 ([11C]T-278) specifically binds to DGKγ and yields a high signal-noise ratio for DGKγ in rodent brains. |
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| 書誌情報 |
Journal of Medicinal Chemistry 巻 64, p. 11990-12002, 発行日 2021-08 |
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| 出版者 | ||||||
| 出版者 | ACS | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-2623 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acs.jmedchem.1c00584 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00584 | |||||
