論文 - 詳細
| RRC ID | 81177 |
|---|---|
| 著者 | Nii T, Hijii S, Kaneko R, Tanito K, Yamanaka K, Kishimura A, Mori T, Katayama Y. |
| タイトル | In vitro evaluation of novel SN-38 prodrug activated by α-rhamnosidase of exogenous enzyme. |
| ジャーナル | Anal Sci |
| Abstract |
This study introduces the α-rhamnose (Rham)-conjugated prodrug of SN-38 (Rham-SN-38) as a promising alternative to irinotecan. α-rhamnosidase, responsible for SN-38 release from Rham-SN-38, does not express in human cells, minimizing individual variability and side effects. The injection of the α-rhamnosidase into the tumor tissues makes it possible, for the first time, to activate the Rham-SN-38. Furthermore, α-rhamnosidase demonstrates significantly higher activity than carboxylesterase, the specific enzyme activating irinotecan. SN-38 release mediated by α-rhamnosidase completes within 2 h, with a kcat/Km value approximately 5.0 × 104-fold higher than that of irinotecan. The 50% inhibition concentration (IC50) of Rham-SN-38 against three types of cancer cells and one normal cell exceeds 4.5 × 103 nM. The addition of α-rhamnosidase significantly increases cytotoxicity, with IC50 comparable to free SN-38. The QIC50, an index reflecting the difference in cytotoxicity with and without α-rhamnosidase, exceeds approximately 1.0 × 102-fold. Rham-SN-38, synthesized in this study, demonstrates significant potential as a prodrug for cancer therapy. |
| 巻・号 | 40(8) |
| ページ | 1529-1535 |
| 公開日 | 2024-8-1 |
| DOI | 10.1007/s44211-024-00593-9 |
| PII | 10.1007/s44211-024-00593-9 |
| PMID | 38748393 |
| MeSH | Cell Line, Tumor Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Glycoside Hydrolases* / antagonists & inhibitors Glycoside Hydrolases* / metabolism Humans Irinotecan* / chemistry Irinotecan* / pharmacology Prodrugs* / chemical synthesis Prodrugs* / chemistry Prodrugs* / metabolism Prodrugs* / pharmacology |
| IF | 2.049 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |