Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology.
Bioorg Med Chem Lett
; 110: 129889, 2024 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-39004318
ABSTRACT
Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 µM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial
/
Bibliotecas de Moléculas Pequenas
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article