Design, Synthesis, and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel PI3K/mTOR Dual Inhibitors.
J Med Chem
; 63(6): 3028-3046, 2020 03 26.
Article
en En
| MEDLINE
| ID: mdl-32069401
ABSTRACT
PI3K-Akt-mTOR signaling pathway has been validated as an effective targeting pathway for cancer therapy. However, no PI3K/mTOR dual inhibitor has been approved by the FDA yet. Therefore, it is still essential to discover a candidate with good efficacy and low toxicity. In our design, a series of imidazo[1,2-a]pyridine derivatives had been synthesized and subjected to activity assessment in vitro and in vivo. 15a was proved to be a potent PI3K/mTOR dual inhibitor with excellent kinase selectivity, modest plasma clearance, and acceptable oral bioavailability. Besides, 15a displayed significant inhibition of tumor growth in HCT116 and HT-29 xenografts without obvious effect on body weight.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Piridinas
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Inhibidores de Proteínas Quinasas
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Serina-Treonina Quinasas TOR
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Inhibidores de las Quinasa Fosfoinosítidos-3
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Imidazoles
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2020
Tipo del documento:
Article