Covalent fragment-based drug discovery for target tractability.
Curr Opin Struct Biol
; 86: 102809, 2024 06.
Article
em En
| MEDLINE
| ID: mdl-38554479
ABSTRACT
An important consideration in drug discovery is the prioritization of tractable protein targets that are not only amenable to binding small molecules, but also alter disease biology in response to small molecule binding. Covalent fragment-based drug discovery has emerged as a powerful approach to aid in the identification of such protein targets. The application of irreversible binding mechanisms enables the identification of fragment hits for challenging-to-target proteins, allows proteome-wide screening in a cellular context, and makes it possible to determine functional effects with modestly potent ligands without the requirement for extensive compound optimization. Here, we provide an overview of recent approaches to covalent fragment-based screening and discuss how these have been applied to establish the tractability of unexplored binding sites on protein targets.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Bibliotecas de Moléculas Pequenas
/
Descoberta de Drogas
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article