| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-12-27 |
| タイトル |
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タイトル |
Development of Novel 11C?Labeled Selective Orexin?2 Receptor Radioligands for Positron Emission Tomography Imaging |
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言語 |
en |
| 言語 |
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|
言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Jian Rong
Yamasaki Tomoteru
Yinlong Li
Kumata Katsushi
Chunyu Zhao
Ahmed Haider
Jiahui Chen
Zhiwei Xiao
Fujinaga Masayuki
Kuan Hu
Mori Wakana
Yiding Zhang
Xie Lin
Xin Zhou
Thomas L. Collier
Zhang Ming-Rong
Steven Liang
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
ABSTRACT: Orexin 2 receptors (OX2R) represent a vital subtype of orexin receptors intricately involved in the regulation of wakefulness, arousal, and sleep?wake cycles. Despite their importance, there are currently no positron emission tomography (PET) tracers available for imaging the OX2R in vivo. Herein, we report [11C]1 ([11C]OX2-2201) and [11C]2 ([11C]OX2-2202) as novel
PET ligands. Both compounds 1 (Ki = 3.6 nM) and 2 (Ki = 2.2 nM) have excellent binding a!nity activities toward OX2R and target selectivity (OX2/OX1 > 600 folds). In vitro autoradiography in the rat brain suggested good to excellent in vitro binding specificity for [11C]1 and [11C]2. PET imaging in rat brains indicated that the low brain uptake of [11C]2 may be due to P-glycoprotein and/or breast cancer resistance protein e"ux interaction and/or low passive permeability. Continuous effort in medicinal chemistry optimization is necessary to improve the brain permeability of this scaffold. |
| 書誌情報 |
ACS Medicinal Chemistry Letters
巻 14,
号 10,
p. 1419-1426,
発行日 2023-09
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| 出版者 |
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出版者 |
American Chemical Society |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1948-5875 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1021/acsmedchemlett.3c00320 |
