Small-molecule "BRCA1-mimetics" are antagonists of estrogen receptor-α.

ABSTRACT:

Context

Resistance to conventional antiestrogens is a major cause of treatment failure and, ultimately, death in breast cancer.

Objective

The objective of the study was to identify small-molecule estrogen receptor (ER)-α antagonists that work differently from tamoxifen and other selective estrogen receptor modulators.

Design

Based on in silico screening of a pharmacophore database using a computed model of the BRCA1-ER-α complex (with ER-α liganded to 17β-estradiol), we identified a candidate group of small-molecule compounds predicted to bind to a BRCA1-binding interface separate from the ligand-binding pocket and the coactivator binding site of ER-α. Among 40 candidate compounds, six inhibited estradiol-stimulated ER-α activity by at least 50% in breast carcinoma ce

SUBMITTER: Ma Y 

PROVIDER: S-EPMC4250363 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature