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Control of Chronic Inflammation with Pathway Selective Estrogen Receptor Ligands

[ Vol. 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   Pages 103 - 111 ( 9 )

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.

Keywords:

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

Affiliation:

Chemical and ScreeningSciences and Women's Health Research Institute, Cardiovascular/MetabolicDiseases, Wyeth Research, 500 Arcola Rd, Collegeville, PA 19426, USA.



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