| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2022-01-28 |
| タイトル |
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タイトル |
Synthesis and fundamental evaluation of radioiodinated rociletinib (CO-1686) as a probe to lung cancer with L858R/T790M mutations of Epidermal Growth Factor Receptor (EGFR) |
| 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 |
| ID登録 |
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ID登録 |
10.24517/00065234 |
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ID登録タイプ |
JaLC |
| 著者 |
Fawwaz, Muammar
Mishiro, Kenji
Nishii, Ryuichi
Sawazaki, Izumi
Shiba, Kazuhiro
Kinuya, Seigo
Ogawa, Kazuma
|
| 著者別表示 |
三代, 憲司
柴, 和弘
絹谷, 清剛
小川, 数馬
|
| 提供者所属 |
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内容記述タイプ |
Other |
|
内容記述 |
金沢大学疾患モデル総合研究センター |
| 書誌情報 |
Molecules
巻 25,
号 12,
p. 2914,
発行日 2020
|
| 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 |
1420-3049 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.3390/molecules25122914 |
| 出版者 |
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出版者 |
MDPI AG |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Rociletinib (CO-1686), a 2,4-diaminopyrimidine derivative, is a highly potent tyrosine kinase inhibitor (TKI) that acts on epidermal growth factor receptor (EGFR) with L858R/T790M mutations. We supposed radioiodinated CO-1686 would function as a useful tool for monitoring EGFR L858R/T790M mutations. To aid in patient selection before therapy with EGFR-TKIs, this study aimed to develop a 125I-labeled derivative of CO-1686, N-{3-[(2-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-4-yl] amino}-5-([125I]iodophenyl)acrylamide ([125I]ICO1686) and evaluate its selectivity toward EGFR L858R/T790M. Radiosynthesis was performed by iododestannylation of the corresponding tributylstannyl precursor with [125I]NaI and N-chlorosuccinimide. The selectivity of the tracer for detecting EGFR L858R/T790M was evaluated using three relevant non-small cell lung cancer (NSCLC) cell lines—H1975, H3255 and H441 overexpressing the dual mutation EGFR L858R/T790M, active mutant EGFR L858R and wild-type EGFR, respectively. The nonradioactive ICO1686 and the precursor compound were successfully synthesized. A novel radiolabeled probe, [125I]ICO1686, was prepared with high radiochemical yield (77%) and purity (>99%). ICO1686 exhibited high cytotoxicity toward H1975 (IC50 0.20 ± 0.05 µM) and H3255 (IC50 0.50 ± 0.21 µM), which is comparable to that of CO-1686. In contrast, the cytotoxicity of ICO1686 toward H441 was 10-fold lower than that toward H1975. In the cell uptake study, the radioactivity uptake of [125I]ICO1686 in H1975 was 101.52% dose/mg, whereas the uptakes in H3255 and H441 were 33.52 and 8.95% dose/mg, respectively. The uptake of [125I]ICO1686 in H1975 was greatly reduced to 45.61% dose/mg protein by treatment with excess CO-1686. In vivo biodistribution study of the radiotracer found that its accumulation in H1975 tumor (1.77 ± 0.43% ID/g) was comparable to that in H3255 tumor (1.63 ± 0.23% ID/g) and the accumulation in H1975 tumor was not reduced by pretreatment with an excess dose of CO-1686. Although this radiotracer exhibited highly specific in vitro uptake in target cancer cells, structural modification is required to improve in vivo biodistribution. © 2020 by the authors. |
| 内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| 権利 |
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権利情報 |
Copyright © author, Published by the MDPI AG |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
http://www.mdpi.com/journal/molecules |
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関連名称 |
http://www.mdpi.com/journal/molecules |
ME-PR-SHIBA-K-25-02914-v2.pdf (1.5 MB)
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