1. Academic Validation
  2. Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity

Identification of pathway-selective estrogen receptor ligands that inhibit NF-kappaB transcriptional activity

  • Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2543-8. doi: 10.1073/pnas.0405841102.
Christopher C Chadwick 1 Susan Chippari Edward Matelan Lisa Borges-Marcucci Amy M Eckert James C Keith Jr Leo M Albert Yelena Leathurby Heather A Harris Ramesh A Bhat Mark Ashwell Eugene Trybulski Richard C Winneker Steven J Adelman Robert J Steffan Douglas C Harnish
Affiliations

Affiliation

  • 1 Women's Health Research Institute and Departmens of Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Abstract

Inflammation is now recognized as a key component in a number of diseases such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease. The transcription factor NF-kappaB has been shown to be involved in both the early and late stages of the inflammatory-proliferative process. In this report, we describe the identification of the pathway-selective Estrogen Receptor (ER) ligand, WAY-169916, that inhibits NF-kappaB transcriptional activity but is devoid of conventional estrogenic activity. This pathway-selective ligand does not promote the classic actions of estrogens such as stimulation of uterine proliferation or ER-mediated gene expression, but is a potent antiinflammatory agent, as demonstrated in the HLA-B27 transgenic rat model of inflammatory bowel disease. Our results indicate the potential utility of pathway-selective ER ligands such as WAY-169916 in the treatment of chronic inflammatory diseases.

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