Erb-041 -: Estrogen receptor (ER) β agonist treatment of endometriosis treatment of rheumatoid arthritis

ERB-041 is a potent and highly selective estrogen receptor (ER) beta agonist that has comparable binding affinity for ER beta as the natural ligand (17 beta-estradiol), but is > 200-fold selective over ER alpha. The development of ERB-041 followed a traditional SAR approach, but those efforts were significantly strengthened by structural information in the form of X-ray co-crystals and molecular modeling. ERB-041 has proven invaluable in validating ER beta as a drug target, and in combination with the ER alpha-selective ligand PPT, has allowed us to dissect the in vivo roles of these two ERs. ERB-041 is inactive in models of classic estrogen action but has dramatic beneficial activity in certain in vivo models of human disease. These include two models of chronic inflammation (HLA-B27 transgenic rats, Lewis rat model of adjuvant-induced arthritis) and the nude mouse model of endometriosis. ERB-041 is in clinical development for endometriosis and rheumatoid arthritis.