In order to gain insight into the structural basis of the observed ERα inhibitory effects of compound 4a, we performed in silico docking analysis using Autodock Vina. Low-energy binding poses were generated by evaluating the combined energetic contributions of torsion, steric repulsion, hydrogen bonding, and hydrophobic interactions between the ligand and the protein binding pocket. Using the crystal structures of ERα in complexes with estradiol [PDB: 1GWR (Warnmark et al., 2002), Figure 3A] and the weak agonists 17α-modified estradiol analogs TFMPV-E2 [PDB: 2P15 (Nettles et al., 2007), Figure 3B] and EEu [PDB: 2YAT (Li et al., 2011), Figure 3C], we found that the steroidal moiety of compound 4a in the docked poses differs from the estradiol moieties of the original ligands (Table 1, Figures 3A–C,E).