Editing Selective estrogen receptor modulator (section)

==== Second-generation benzothiophenes ====
[[File:Raloxifene AnDring.png|thumb|385x385px|class=skin-invert-image|"A ring" (A) and "D ring" (D) marked in raloxifene.]]

Raloxifene, like 4-hydroxytamoxifen, binds to ERα with the hydroxyl group of its phenolic "A ring" through hydrogen bonds with Arg-394 and Glu-353. In addition to these bonds, raloxifene forms a second hydrogen bond to ER through the side group of His-524 because of the presence of a second hydroxyl group in the "D ring". This hydrogen bond is also unlike that between 17β-estradiol and His-524, as the [[imidazole ring]] of His-524 is rotated to counteract the difference of the oxygen position in raloxifene and in 17β-estradiol. Just like in 4-hydroxytamoxifen, the bulky side chain of raloxifene displaces helix 12.<ref name=Rosano_2011 />