論文 - 詳細
| RRC ID | 77552 |
|---|---|
| 著者 | Sima L, Wang Z, Yu L, Hou Y, Zhao D, Luo B, Liao W, Liu X. |
| タイトル | Discovery of LAH-1 as potent c-Met inhibitor for the treatment of non-small cell lung cancer. |
| ジャーナル | J Enzyme Inhib Med Chem |
| Abstract |
ABSTRCTDysregulated HGF/c-Met pathway has been implicated in multiple human cancers and has become an attractive target for cancer intervention. Herein, we report the discovery of N-(3-fluoro-4-((2-(3-hydroxyazetidine-1-carboxamido)pyridin-4-yl)oxy)phenyl)-1-(4-fluorophenyl)-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxamide (LAH-1), which demonstrated nanomolar MET kinase activity as well as desirable antiproliferative activity, especially against EBC-1 cells. Mechanism studies confirmed the effects of LAH-1 on modulation of HGF/c-Met pathway, induction of cell apoptosis, inhibition on colony formation as well as cell migration and invasion. In addition, LAH-1 also showed desirable in vitro ADME properties as well as acceptable in vivo PK parameters. The design, synthesis, and characterisation of LAH-1 are described herein. |
| 巻・号 | 39(1) |
| ページ | 2286435 |
| 公開日 | 2024-12-1 |
| DOI | 10.1080/14756366.2023.2286435 |
| PMID | 38078363 |
| PMC | PMC11721924 |
| MeSH | Carcinoma, Non-Small-Cell Lung* / drug therapy Cell Line, Tumor Cell Proliferation Humans Lung Neoplasms* / drug therapy Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-met |
| IF | 4.673 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 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 | EBC-1(RCB1965) |