Discovery of benzodioxane analogues as lead candidates of AIMP2-DX2 inhibitors.
Bioorg Med Chem Lett
; 73: 128889, 2022 10 01.
Article
em En
| MEDLINE
| ID: mdl-35842206
ABSTRACT
Aminoacyl-tRNA synthetase (ARS) interacting multifunctional protein2 (AIMP2) plays a vital role in protein synthesis. However, a splicing variant in which the second of the four exons of AIMP2 is deleted, inhibits the tumor suppression activity of AIMP2. Herein, we describe our discovery of series of potent AIMP2-DX2 inhibitors that are targeting lung cancer. Optimization of series using ligand-based drug design strategy led to discovery of compound 35, a potent AIMP2-DX2 inhibitor that is the most efficacious in H460 and A549 cells. This benzodioxane series may represent good starting points for further lead optimization of the identification potential drug candidates for the AIMP2-DX2 targeted treatment of lung cancer.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Aminoacil-tRNA Sintetases
/
Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article