Strengthening Molecular Glues: Design Strategies for Improving Thalidomide Analogs as Cereblon Effectors and Anticancer Agents.
Drug Discov Today
; 29(6): 104010, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38704021
ABSTRACT
In the two decades since a novel thalidomide analog was last approved, many promising drug candidates have emerged with remarkable potency as targeted protein degraders. Likewise, the advent of PROTACs for suppressing 'undruggable' protein targets reinforces the need for new analogs with improved cereblon affinity, target selectivity and drug-like properties. However, thalidomide and its approved derivatives remain plagued by several shortcomings, such as structural instability and poor solubility. Herein, we present a review of strategies for mitigating these shortcomings and highlight contemporary drug discovery approaches that have generated novel thalidomide analogs with enhanced efficacy as cereblon effectors and/or anticancer agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Talidomida
/
Diseño de Fármacos
/
Ubiquitina-Proteína Ligasas
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Drug Discov Today
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article