Background:

ERA63 is a selective estrogen receptor α agonist.

The pharmacologic properties for the ERα agonist ERA-63 (Org 37663) have been shown efficacy in inflammatory models at 1.5 mg/kg. ERA-63 dose-dependently decreases the TT-specific response whereas treatment with the ERβ-agonist ERB-79 has no effect on TT-specific swelling. ERA-63 inhibits the tetanus toxoid (TT)-specific DTH response in WT and ERβ-/- mice but not in ERα-/- mice. ERA-63 inhibits the tetanus-specific delayed type hypersensitivity response in WT and ERβKO but not in the ERαKO mice. Therapeutic administration of the selective agonist ERA-63 decreases the clinical signs of arthritis dose-dependently. In addition, the AUC analysis over the 20-day treatment period reveals a significant dose-dependent reduction in the ERA-63-treated mice when compared with vehicle control[1]. After 28 days of treatment with dosages ranging from pharmacological up to clearly toxic levels, selected ERA-63 dose levels (0.167-0.2, 1.67-2 and 16.7-20 mg/kg) are expected to have comparable estrogenic activity to respective EE dose levels (0.05, 0.5 and 5 mg/kg)[2].

[1]. Dulos J, et al. Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor alpha but not estrogen receptor beta. Arthritis Res Ther. 2010;12(3):R101. [2]. Janssen GB, et al. The evaluation of the immunomodulating properties of ERA-63 a pharmaceutical with estrogenic activity. Toxicol Lett. 2008 Aug 28;180(3):196-201.