Figure 1. Chemical structures of planar estrogens, angular estrogens, SERMS, and ShERPAs.

The box (in green) highlights the benzothiophene scaffold embedded in raloxifene and arzoxifene structures, of which the ShERPAs’ structures were based upon. The continuous box (in yellow) highlights the phenyl ring bearing OH of triphenylethylenes (TPEs): trihydroxytriphenylethylene (3OHTPE) and BPTPE (46), which makes them angular estrogens/partial agonists. The dashed box (in brown) highlights the absence of OH on the phenyl ring of the Z-isomer of dihydroxytriphenylethylene (Z2OHTPE), which makes it an angular estrogen/full agonist like E₂ and diethylstilbestrol (DES) (46).