Preclinical characterization of selective estrogen receptor beta agonists: new insights into their therapeutic potential.

It has now been over 10 years since Jan-Ake Gustafsson revealed the existence of a second form of the estrogen receptor (ERbeta) at a 1996 Keystone Symposium. Since then, substantial success has been made in distinguishing its potential biological functions from the previously known form (now called ERalpha) and how it might be exploited as a drug target. Subtype selective agonists have been particularly useful in this regard and suggest that ERbeta agonists may be useful for a variety of clinical applications without triggering classic estrogenic side effects such as uterine stimulation. These applications include inflammatory bowel disease, rheumatoid arthritis, endometriosis, and sepsis. This manuscript will summarize illustrative data for three ERbeta selective agonists, ERB-041, WAY-202196, and WAY-200070.