Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC).
Biochem Biophys Res Commun
; 505(2): 542-547, 2018 10 28.
Article
em En
| MEDLINE
| ID: mdl-30274779
ABSTRACT
Recently, proteolysis targeting chimera (PROTAC) technology is highlighted in drug discovery area as a new therapeutic approach. PROTAC as a heterobifunctional molecule is comprised of two ligands, which recruit target protein and E3 ligase, respectively. To degrade the anaplastic lymphoma kinase (ALK) fusion protein, such as NPM-ALK or EML4-ALK, we generated several ALK-PROTAC molecules consisted of ceritinib, one of the ALK inhibitors, and ligand of von Hippel-Lindau (VHL) E3 ligase. Among these molecules, TD-004 effectively induced ALK degradation and inhibited the growth of ALK fusion positive cell lines, SU-DHL-1 and H3122. We also confirmed that TD-004 significantly reduced the tumor growth in H3122 xenograft model.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Proteínas Quinases
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Quinase do Linfoma Anaplásico
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article