Innovative, combinatorial and high-throughput approaches to degrader synthesis.
Chem Soc Rev
; 53(10): 4838-4861, 2024 May 20.
Article
em En
| MEDLINE
| ID: mdl-38596888
ABSTRACT
Targeted protein degraders such as PROTACs and molecular glues are a rapidly emerging therapeutic modality within industry and academia. Degraders possess unique mechanisms of action that lead to the removal of specific proteins by co-opting the cell's natural degradation mechanisms via induced proximity. Their optimisation thus far has often been largely empirical, requiring the synthesis and screening of a large number of analogues. In addition, the synthesis and development of degraders is often challenging, leading to lengthy optimisation campaigns to deliver candidate-quality compounds. This review highlights how the synthesis of degraders has evolved in recent years, in particular focusing on means of applying high-throughput chemistry and screening approaches to expedite these timelines, which we anticipate to be valuable in shaping the future of degrader optimisation campaigns.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Química Combinatória
/
Ensaios de Triagem em Larga Escala
Idioma:
En
Revista:
Chem Soc Rev
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido