An overview of PROTACs targeting MDM2 as a novel approach for cancer therapy.
Eur J Med Chem
; 272: 116506, 2024 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-38761584
ABSTRACT
MDM2 genes amplification or altered expression is commonly observed in various cancers bearing wild-type TP53. Directly targeting the p53-binding pocket of MDM2 to activate the p53 pathway represents a promising therapeutic approach. Despite the development of numerous potent MDM2 inhibitors that have advanced into clinical trials, their utility is frequently hampered by drug resistance and hematologic toxicity such as neutropenia and thrombocytopenia. The emergence of PROTAC technology has revolutionized drug discovery and development, with applications in both preclinical and clinical research. Harnessing the power of PROTAC molecules to achieve MDM2 targeted degradation and p53 reactivation holds significant promise for cancer therapy. In this review, we summarize representative MDM2 PROTAC degraders and provide insights for researchers investigating MDM2 proteins and the p53 pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-mdm2
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Neoplasias
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China