In silico discovery and validation of potent small-molecule inhibitors targeting the activation function 2 site of human oestrogen receptor α.

ABSTRACT:

Introduction

Current approaches to inhibit oestrogen receptor-alpha (ERα) are focused on targeting its hormone-binding pocket and have limitations. Thus, we propose that inhibitors that bind to a coactivator-binding pocket on ERα, called activation function 2 (AF2), might overcome some of these limitations.

Methods

In silico virtual screening was used to identify small-molecule ERα AF2 inhibitors. These compounds were screened for inhibition of ERα transcriptional activity using stably transfected T47D-KBluc cell line. A direct physical interaction between the AF2 binders and the ERα protein was measured using biolayer interferometry (BLI) and an ERα coactivator displacement assay. Cell viability was assessed by MTS assay in ERα-positive MCF7 cells, tamoxifen-resistant (TamR

SUBMITTER: Singh K 

PROVIDER: S-EPMC4360945 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature