In Silico Discovery and Validation of Potent Small-Molecule Inhibitors Targeting the Activation Function 2 Site of Human Oestrogen Receptor α

Singh K, et al., 17:27, Breast Cancer Res, 2015

Described herein is the identification of more potent and selective small-molecule inhibitors for a coactivator-binding pocket on oestrogen receptor-alpha (Erα). Commonly known as the activation function 2 (AF2), the interaction between AF2-binders, and the ERα protein were analyzed by Bio-Layer Interferometry (BLI) using a Pall ForteBio Octet RED instrument equipped with Super Streptavidin biosensors. Fifteen inhibitors of ERα AF2 were identified from this study out of which, the inhibitor VPC-16230 was identified as the lead ERα AF2 inhibitor demonstrating a substantial down regulation of ERα transcriptional activity.

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