| Description: |
LY500307 shows potent binding affinity For both ERα (Ki 2.68 nM) and ERβ (Ki 0.19 nM), which exhibits 14-fold binding selectivity For the β iso Form, generated using 3H-estradiol and recombinant, full-length, human ERs in a competitive binding assay. LY500307 shows full agonist function in both ERα and ERβ assays (>90% relative efficacy), displays potent inhibition toward ERβ with EC50 of 0.66 nM exhibiting 32 fold specificity For ERβ than For ERα which has EC50 of 19.4 nM measured using a transcription assay in the cotransfected human prostate cancer PC3/ER (α or β)-ERE cell line. LY500307/ERα and LY500307/ERβ X-ray cocrystal structures show significant differences in the manner in which LY500307 binds within the binding pockets. LY500307 displays a different orientation corresponding to a (ca. 180°) rotation on its bisphenol axis, and the A ring phenol of LY500307, while bound to histidine in both structures, locates to different sides of the imidazole functionality For this interaction explaining the observed selectivity of LY500307 For ERβ. 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. For the detailed information of LY500307, the solubility of LY500307 in water, the solubility of LY500307 in DMSO, the solubility of LY500307 in PBS buffer, the animal experiment (test) of LY500307, the cell expriment (test) of LY500307, the in vivo, in vitro and clinical trial test of LY500307, the EC50, IC50,and Affinity of LY500307, Please contact DC Chemicals. |
