Estrogen receptor modulator review

Abstract

The past few years have seen considerable advances in the development of estrogen receptor (ER) modulators and in the understanding of their interaction on estrogen pathways. Whilst prototypical steroidal estrogen agonists have long been appreciated for their use in female contraception and estrogen replacement therapy, more recent investigations have focused on subtype estrogen receptor modulators with selectivity for use in rapidly expanding treatment modalities. As estrogenic effects are primarily mediated through two receptors, defined as ERα and ERβ, significant interest has been dedicated to identifying subtype-selective agonists, antagonists and selective estrogen receptor modulators (SERMs). Additional effort has been dedicated to finding non-subtype-selective SERMs with new utility or improved profiles. Many of these recently identified ligands represent real advances in terms of their preclinical profile with the potential to one day provide novel treatments. This review highlights recent developments on the structural and biological data reported for ER modulators in the patent and scientific literature during the period 2003 – 2005.

Keywords::

• estrogen
• estrogen receptor-α
• estrogen receptor-β
• selective estrogen receptor modulator (SERM)
• SERAM

Acknowledgement

The authors thank Drs. H Harris, R Mewshaw and R Bernotas for valuable criticism of the manuscript, Drs. G Trybulski and D Harnish for input with ER NF-κB, as well as R Morris for proofreading the manuscript.