Discovery of a Phosphoinositide 3-Kinase (PI3K) ß/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kß Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856.
J Med Chem
; 60(4): 1555-1567, 2017 02 23.
Article
em En
| MEDLINE
| ID: mdl-28106991
ABSTRACT
Phosphoinositide 3-kinase (PI3K) ß signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation of a novel series of PI3Kß/δ inhibitors in which PI3Kß potency was built in a PI3Kδ-selective template. This work led to the discovery of a highly selective PI3Kß/δ inhibitor displaying excellent pharmacokinetic profile and efficacy in a human PTEN-deficient LNCaP prostate carcinoma xenograft tumor model.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Inibidores de Proteínas Quinases
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PTEN Fosfo-Hidrolase
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Inibidores de Fosfoinositídeo-3 Quinase
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article