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A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.
Patel, Hitisha K; Siklos, Marton I; Abdelkarim, Hazem; Mendonca, Emma L; Vaidya, Aditya; Petukhov, Pavel A; Thatcher, Gregory R J.
Afiliación
  • Patel HK; Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, UIC, 833 S. Wood St., Chicago, IL 60612-7231 (USA).
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 type I HDAC isoforms and antagonism of estrogenic activity in two cell lines yielded a SERMostat with 1-3 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.
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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

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