A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.
ChemMedChem
; 9(3): 602-13, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-23956109
ABSTRACT
Breast cancer remains a significant cause of death in women, and few therapeutic options exist for estrogen receptor negative (ER (-)) cancers. Epigenetic reactivation of target genes using histone deacetylase (HDAC) inhibitors has been proposed in ER (-) cancers to resensitize to therapy using selective estrogen receptor modulators (SERMs) that are effective in ER (+) cancer treatment. Based upon preliminary studies in ER (+) and ER (-) breast cancer cells treated with combinations of HDAC inhibitors and SERMs, hybrid drugs, termed SERMostats, were designed with computational guidance. Assay for inhibition of four typeâ
I HDAC isoforms and antagonism of estrogenic activity in two cell lines yielded a SERMostat with 1-3â
µM potency across all targets. The superior hybrid caused significant cell death in ER (-) human breast cancer cells and elicited cell death at the same concentration as the parent SERM in combination treatment and at an earlier time point.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Moduladores Selectivos de los Receptores de Estrógeno
/
Inhibidores de Histona Desacetilasas
/
Antineoplásicos
Tipo de estudio:
Guideline
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2014
Tipo del documento:
Article