Control of Chronic Inflammation with Pathway Selective Estrogen Receptor Ligands

Title: Control of Chronic Inflammation with Pathway Selective Estrogen Receptor Ligands

Volume: 6 Issue: 2

Author(s): Robert J. Steffan, Edward Matelan, Mark A. Ashwell, William J. Moore, William R. Solvibile, Eugene Trybulski, Christopher C. Chadwick, Susan Chippari, Thomas Kenney, Richard C. Winneker, Amy Eckert, Lisa Borges-Marcucci, Steven J. Adelman, Zhang Xu, Lydia Mosyak and Douglas C. Harnish

Affiliation:

Keywords: Estrogen receptor, ER, nuclear factor kappa B, NF-kB

Abstract: The discovery of novel intervention points in the inflammatory pathway has been a focus of drug development in recent years. We have identified pathway selective ligands for the estrogen receptor (ER) that inhibit NF-kB mediated inflammatory gene expression causing a reduction of cytokines, chemokines, adhesion molecules and inflammatory enzymes. SAR development of a series of 4-(Indazol-3-yl)-phenols has led to the identification of WAY-169916 an orally active non-steroidal ligand with the potential use in the treatment of inflammatory diseases without the classical proliferative effects associated with non-selective estrogens.

Cite this article as:

Steffan J. Robert, Matelan Edward, Ashwell A. Mark, Moore J. William, Solvibile R. William, Trybulski Eugene, Chadwick C. Christopher, Chippari Susan, Kenney Thomas, Winneker C. Richard, Eckert Amy, Borges-Marcucci Lisa, Adelman J. Steven, Xu Zhang, Mosyak Lydia and Harnish C. Douglas, Control of Chronic Inflammation with Pathway Selective Estrogen Receptor Ligands, Current Topics in Medicinal Chemistry 2006; 6 (2) . https://dx.doi.org/10.2174/156802606775270279