way-169916 and Inflammatory-Bowel-Diseases

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.

Topics: Animals; Animals, Genetically Modified; Cell Line; Estrogen Receptor alpha; Estrogen Receptor beta; Female; HLA-B27 Antigen; Humans; Inflammatory Bowel Diseases; Ligands; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Pyrazoles; Rats; Receptors, Estrogen; Transcription, Genetic; Uterus