Editing Selective estrogen receptor modulator (section)

==== First-generation triphenylethylenes ====
Tamoxifen is converted by the liver [[cytochrome P450]] into the 4-hydroxytamoxifen<ref name=Rosano_2011 /> and is a more selective antagonist of the ERα subtype than ERβ.<ref name="Taneja_2006">{{cite journal | vauthors = Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA | title = Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy | journal = Expert Opinion on Investigational Drugs | volume = 15 | issue = 3 | pages = 293–305 | date = Mar 2006 | pmid = 16503765 | doi = 10.1517/13543784.15.3.293 | s2cid = 29510508 }}</ref> 4-hydroxytamoxifen binds to ERs within the same binding pocket that recognizes 17β-estradiol. The receptor recognition of 4-hydroxytamoxifen appears to be controlled by two structural features of 4-hydroxytamoxifen, the phenolic A ring, and the bulky side chain. The phenolic A ring forms hydrogen bonds to the side groups of ER's Arg-394, Glu-354 and to structurally conserved water. The bulky side chain, protruding from the binding cavity, displaces helix 12 from ligand-binding pocket to cover part of the coactivator binding pocket. The ER-4-hydroxytamoxifen complex formation recruits corepressors proteins. This leads to decreased DNA synthesis and inhibition of estrogen activity.<ref name=Rosano_2011 /> Clomifene and torimefene produce binding affinities similar to that of tamoxifen.<ref name="Fang_2001"/> Thus, these two drugs are more selective antagonists of the ERα subtype than ERβ.<ref name="Taneja_2006" />