Reference - Detail
| RRC ID | 81177 |
|---|---|
| Author | Nii T, Hijii S, Kaneko R, Tanito K, Yamanaka K, Kishimura A, Mori T, Katayama Y. |
| Title | In vitro evaluation of novel SN-38 prodrug activated by α-rhamnosidase of exogenous enzyme. |
| Journal | 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. |
| Volume | 40(8) |
| Pages | 1529-1535 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | A549(RCB0098) |