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A novel polyethylene glycol (PEG)-drug conjugate of Venetoclax, a Bcl-2 inhibitor, for treatment of acute myeloid leukemia (AML)
https://tokushima-u.repo.nii.ac.jp/records/2009408
https://tokushima-u.repo.nii.ac.jp/records/2009408b043e751-1e21-49b4-9bed-6bf4fd8ca48f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
cnr_5_3_e1485.pdf (1.37 MB)
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| Item type | 文献 / Documents(1) | |||||||||||||||||||||||||||||
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| 公開日 | 2021-12-07 | |||||||||||||||||||||||||||||
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| アクセス権 | open access | |||||||||||||||||||||||||||||
| 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 | |||||||||||||||||||||||||||||
| 出版社版DOI | ||||||||||||||||||||||||||||||
| 関連識別子 | https://doi.org/10.1002/cnr2.1485 | |||||||||||||||||||||||||||||
| 関連名称 | 10.1002/cnr2.1485 | |||||||||||||||||||||||||||||
| 出版タイプ | ||||||||||||||||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||||||||||||||||
| タイトル | ||||||||||||||||||||||||||||||
| タイトル | A novel polyethylene glycol (PEG)-drug conjugate of Venetoclax, a Bcl-2 inhibitor, for treatment of acute myeloid leukemia (AML) | |||||||||||||||||||||||||||||
| 著者 |
安藤, 英紀
× 安藤, 英紀
WEKO
700
× ムラカミ, ユウタ
× エシマ, キヨシ
× 石田, 竜弘
WEKO
1145
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| 内容記述 | Background: Venetoclax (VTX) is an anticancer drug. It is a selective Bcl-2 inhibitor that is clinically used for the treatment of patients with lymphomas and leukemias. Treatment with VTX, however, is accompanied by severe adverse events such as tumor lysis syndrome and neutropenia, because VTX readily binds to serum proteins, which results in poor pharmacokinetics and poor tumor tissue concentration. To avoid such adverse events, VTX is administered using a daily or weekly ramp-up schedule that is cumbersome in clinical situations. Aims: To overcome these shortcomings, we prepared a novel polyethylene glycol (PEG)-drug conjugate of VTX (PEG-VTX) and evaluated its cytotoxic effects on acute myeloid leukemia (AML) both in vitro and in vivo. Methods and results: VTX and 4-armed PEG derivatives were covalently attached through an amide bond linker. In a series of in vitro studies, PEG-VTX selectively induced potent growth inhibition of MV4-11 human AML cells via the inducement of Bcl-2-mediated apoptosis. PEG-VTX had the effect of free VTX, presumably due to the protease-mediated release of VTX from the conjugates. In in vivo studies with AML tumor-xenograft mice models, intravenous PEG-VTX promoted sufficient tumor growth suppression. Compared with a regimen of oral free VTX, the intravenous regimen in those studies used a VTX dosage that was 15–30 times smaller for an OCI-AML-2 xenograft model and a dosing regimen that was less frequent for an MV4-11 xenograft model. The most important development, however, was the absence of weight loss related to severe side effects throughout the treatments. An increase in water solubility and the resultant hydrodynamic size of VTX via PEGylation improved the pharmacokinetics of VTX by avoiding protein interactions and lessening the extravasation from blood. The result was an increase in tumor accumulation and a decrease in the nonspecific distribution of VTX. Conclusion: The results of this study suggest that PEG-VTX could be an alternative therapeutic option for the safe and effective treatment of patients with AML. |
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| キーワード | ||||||||||||||||||||||||||||||
| 主題 | acute myeloid leukemia (AML) | |||||||||||||||||||||||||||||
| キーワード | ||||||||||||||||||||||||||||||
| 主題 | PEG-drug conjugate | |||||||||||||||||||||||||||||
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| 主題 | polyethylene glycol (PEG) | |||||||||||||||||||||||||||||
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| 主題 | Venetoclax | |||||||||||||||||||||||||||||
| 書誌情報 |
en : Cancer Reports 巻 5, 号 3, p. e1485, 発行日 2021-06-26 |
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| 収録物識別子タイプ | ISSN | |||||||||||||||||||||||||||||
| 収録物識別子 | 25738348 | |||||||||||||||||||||||||||||
| 出版者 | ||||||||||||||||||||||||||||||
| 出版者 | Wiley Periodicals | |||||||||||||||||||||||||||||
| 権利情報 | ||||||||||||||||||||||||||||||
| 権利情報 | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | |||||||||||||||||||||||||||||
| EID | ||||||||||||||||||||||||||||||
| 識別子 | 375994 | |||||||||||||||||||||||||||||
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| 言語 | eng | |||||||||||||||||||||||||||||
