LY500307 can potently inhibit ER-alpha and ER-beta with Ki of 2.68 nM and 0.19 nM. LY500307 shows 14-fold binding selectivity for the beta isoform. LY500307/ER-alpha and LY500307/ER-beta X-ray cocrystal structures show significant differences in the manner in which LY500307 binds within the binding pockets. [1]
In vivo
Oral administration of LY500307 (0.01-0.05 mg/kg) in CD-1 mice produces the reduction on prostate weights in a dose-response manner, has no effect on testes and SV weights in this dose range and no effect on T and DHT levels at up to 10% the minimum efficacy dose (0.1 mg/kg), while the nonselective ER agonist diethylstilbestrol (DES) shows significant regression of prostate, testes, and SV and also lowering T and DHT. [1]