Development of small-molecule inhibitors that target PI3Kß.
Drug Discov Today
; 29(1): 103854, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-38070704
ABSTRACT
Phosphatidylinositol-3 kinase (PI3K) ß, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kß-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kß, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kß, or using atropisomerism to lock conformation. In this review, we focus on advances in the development of these ß-isoform-selective PI3K inhibitors, providing potential guidance for the further development of novel clinical candidates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
/
Inibidores de Proteínas Quinases
Limite:
Humans
/
Male
Idioma:
En
Revista:
Drug Discov Today
Ano de publicação:
2024
Tipo de documento:
Article