A mutant selective anti-estrogen is a pure antagonist on EREs and AP-1 response elements.

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Jain D, Koh JT

A mutant selective anti-estrogen is a pure antagonist on EREs and AP-1 response elements.

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5258-61. doi: 10.1016/j.bmcl.2010.06.151. Epub 2010 Jul 24.

PubMed ID
20659801 [ View in PubMed
]
Abstract

Estrogen receptors (ERs) regulate gene transcription through classic estrogen response elements (EREs) as well as AP-1 responsive genes. The common SERMs Raloxifene, Tamoxifen, and ICI164384 function as ER antagonists on EREs but as ERbeta agonists/partial agonists on AP-1 responsive genes. While developing a mutant selective analog of Raloxifene, that is an antagonist of ERalpha(E353A), we discovered an antagonist of wild-type ERalpha and ERbeta that is also an antagonist of ERbeta/AP-1 response. The analog, DRL527, represses basal AP-1 gene expression and antagonizes Raloxifene stimulated AP-1 expression. Therefore DRL527 has a unique, previously unreported, ERE/AP-1 activity profile.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
RaloxifeneEstrogen receptor alphaIC 50 (nM)0.3N/AN/ADetails
RaloxifeneEstrogen receptor betaIC 50 (nM)6.9N/AN/ADetails