論文 - 詳細
| RRC ID | 81907 |
|---|---|
| 著者 | Watanabe D, Hiroshima M, Yasui M, Ueda M. |
| タイトル | Single molecule tracking based drug screening. |
| ジャーナル | Nat Commun |
| Abstract |
The single-molecule tracking of transmembrane receptors in living cells has provided significant insights into signaling mechanisms, such as mobility and clustering upon their activation/inactivation, making it a potential screening method for drug discovery. Here we show that single-molecule tracking-based screening can be used to explore compounds both detectable and undetectable by conventional methods for disease-related receptors. Using an automated system for a fast large-scale single-molecule analysis, we screen for epidermal growth factor receptor (EGFR) from 1134 of FDA approved drugs. The 18 hit compounds include all EGFR-targeted tyrosine kinase inhibitors (TKIs) in the library that suppress any phosphorylation-dependent mobility shift of EGFR, proving the concept of this approach. The remaining hit compounds are not reported as EGFR-targeted drugs and do not inhibit EGF-induced EGFR phosphorylation. These non-TKI compounds affect the mobility and/or clustering of EGFR without EGF and induce EGFR internalization, to impede EGFR-dependent cell growth. Thus, single-molecule tracking provides an alternative modality for discovering therapeutics on various receptor functions with previously untargeted mechanisms. |
| 巻・号 | 15(1) |
| ページ | 8975 |
| 公開日 | 2024-10-17 |
| DOI | 10.1038/s41467-024-53432-w |
| PII | 10.1038/s41467-024-53432-w |
| PMID | 39420015 |
| PMC | PMC11486946 |
| MeSH | Cell Line, Tumor Cell Proliferation / drug effects Drug Discovery / methods Drug Evaluation, Preclinical / methods Epidermal Growth Factor / metabolism Epidermal Growth Factor / pharmacology ErbB Receptors* / antagonists & inhibitors ErbB Receptors* / metabolism Humans Phosphorylation / drug effects Protein Kinase Inhibitors* / pharmacology Signal Transduction / drug effects Single Molecule Imaging* / methods |
| IF | 12.121 |
| 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 | 27 |
| 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 | CHO-K1(RCB0285) HeLa((RCB0007) A431(RCB0202) Ba/F3(RCB4476) |