Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Bases de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Bioorg Chem ; 143: 107078, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38181661

RESUMEN

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2. We developed a potent and effective EZH2 degrader P4, which effectively induced EZH2 protein degradation and inhibited breast cancer cell growth. Further studies showed that P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G0/G1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. Therefore, P4 is a potential anticancer molecule for breast cancer treatment.


Asunto(s)
Neoplasias de la Mama , Proteína Potenciadora del Homólogo Zeste 2 , Quimera Dirigida a la Proteólisis , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Proteína Potenciadora del Homólogo Zeste 2/efectos de los fármacos , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Inhibidores Enzimáticos/farmacología , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/farmacología , Quimera Dirigida a la Proteólisis/química , Quimera Dirigida a la Proteólisis/farmacología
2.
ACS Med Chem Lett ; 15(9): 1516-1525, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39291032

RESUMEN

In recent years, it has been proposed that c-mesenchymal-to-epithelial transition factor (c-Met) and histone deacetylase (HDAC) dual inhibition is a promising cancer treatment strategy. Herein, a series of c-Met/HDAC dual inhibitors were designed and synthesized given their synergistic anticancer effect in breast cancer cells. Compound 12d exhibited excellent inhibitory activity against c-Met (IC50 = 28.92 nM) and HDAC (85.68%@1000 nM) and inhibited the proliferation of all three breast cancer cell lines. Moreover, a mechanism investigation demonstrated that 12d could simultaneously induce cell cycle arrest in the G0/G1 phase and cell apoptosis in MDA-MB-231 cells, which was endorsed by c-Met and HDAC pathway blockade. It could also suppress cell invasion. Our results suggest that developing promising c-Met/HDAC dual inhibitors is a novel strategy for breast cancer therapy.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA