Discovery of a novel covalent CDK4/6 inhibitor based on palbociclib scaffold.
Eur J Med Chem
; 219: 113432, 2021 Jul 05.
Article
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| MEDLINE
| ID: mdl-33857728
ABSTRACT
Cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved in dynamic regulation of cell cycle, play an indispensable role in controlling the tumor growth. Here, based on the scaffold of palbociclib, we designed and synthesized a series of covalent CDK4/6 inhibitors that targeted amino acid Thr107. The optimized compound C-13 exhibited potent in vitro anticancer activity against CDK4/6 with high selectivity over CDK4/6. Moreover, C-13 showed significant tumor growth inhibition in MDA-MB-231 tumor xenograft model (TGI of 93.49% at dose of 40 mg/kg) without causing significant weight loss and toxicity during the treatment period.
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Base de datos:
MEDLINE
Asunto principal:
Piperazinas
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Piridinas
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Diseño de Fármacos
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Inhibidores de Proteínas Quinasas
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Quinasa 4 Dependiente de la Ciclina
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Quinasa 6 Dependiente de la Ciclina
Idioma:
En
Revista:
Eur J Med Chem
Año:
2021
Tipo del documento:
Article