Discovery of a potent EGFR and ALK dual mutation inhibitor containing N-(3-((4-((2-(cyclopropylsulfinyl)phenyl)amino)pyrimidin-2-yl)amino) phenyl)acrylamide scaffold.
Bioorg Chem
; 129: 106188, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36220003
ABSTRACT
A series of EGFR and ALK dual inhibitors containing sulfoxide and cyclopropyl groups were designed and synthesized. The lead compound 8a showed a significant activity against EGFR and ALK in both the enzymatic and cellular assays. The study of anti-tumor mechanism indicated that 8a could effectively block the phosphorylation of EGFR and ALK proteins, so as to effectively inhibiting the proliferation and inducing apoptosis of H1975 tumor cells, blocking the cell cycle and reducing the mitochondrial membrane potential inhibited the migration of H1975 cells. In vivo studies, compounds 8a and 8d can significantly subside the tumor tissue of nude mice without obvious toxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores ErbB
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2022
Tipo de documento:
Article