| 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 |
2023-1-1
|
| DOI |
10.1080/14756366.2023.2286435
|
| PMID |
38078363
|
| 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
|
| リソース情報 |
| ヒト・動物細胞 |
EBC-1(RCB1965) |
