WAY-169916 is a pathway-selective estrogen receptor (ER) ligand.¹It binds to human ERα and ERβ (IC₅₀= 3 nM for both) and inhibits IL-1β-induced NF-κB reporter activity in HAECT-1 cells expressing human ERα (IC₅₀= 93 nM), but not cells lacking ER expression, when used at concentrations up to 10 µM. WAY-169916 (1 µM) reduces increases in creatine kinase (CK) activity induced by the ER agonist 17β-estradiol in HAECT-1 cells.In vivo, WAY-169916 (10 mg/kg per day) reduces high-fat diet-induced hepatic NF-κB activity and inflammatory gene expression without increasing uterine weight in ovariectomized rats. It inhibits chronic diarrhea, as well as intestinal ulceration and inflammatory cell infiltration, in an HLA-B27 transgenic rat model of inflammatory bowel disease (IBD). WAY-169916 (1 mg/kg) reduces infarct size in an ovariectomized rabbit model of coronary artery occlusion-induced ischemia and reperfusion injury.²

1.Chadwick, C.C., Chippari, S., Matelan, E., et al.Identification of pathway-selective estrogen receptor ligands that inhibit NF-κB transcriptional activityProc. Natl. Acad. Sci. U.S.A.102(7)2543-2548(2005) 2.Booth, E.A., Marchesi, M., Knittel, A.K., et al.The pathway-selective estrogen receptor ligand WAY-169916 reduces infarct size after myocardial ischemia and reperfusion by an estrogen receptor dependent mechanismJ. Cardiovasc. Pharmacol.49(6)401-407(2007)