Phenotypic screening with target identification and validation in the discovery and development of E3 ligase modulators.
Cell Chem Biol
; 28(3): 283-299, 2021 03 18.
Article
en En
| MEDLINE
| ID: mdl-33740433
ABSTRACT
The use of phenotypic screening was central to the discovery and development of novel thalidomide analogs, the IMiDs (immunomodulatory drugs) agents. With the discovery that these agents bind the E3 ligase, CRL4CRBN, and alter its substrate specificity, there has been a great deal of endeavor to discover other small molecules that can modulate alternative E3 ligases. Furthermore, the chemical properties necessary for drug discovery and the rules by which neo-substrates are selected for degradation are being defined in the context of phenotypic alterations in specific cellular systems. This review gives a detailed summary of these recent advances and the methodologies being exploited to understand the mechanism of action of emerging protein degradation therapies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ubiquitina-Proteína Ligasas
/
Desarrollo de Medicamentos
/
Factores Inmunológicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido