Editing Selective estrogen receptor modulator (section)

==== Third-generation ====
Lasofoxifene interaction with ERα is typical of those between SERM-ERα such as a nearly planar [[topology]] (the tetrahydronapthalene carbocycle), hydrogen bonding with Arg-394 and Glu-353 and the phenyl side chains of lasofoxifene filling the C-ring and D-ring volume of the ligand-binding pocket. Lasofoxifene diverts helix 12 and prevents the binding of coactivator proteins with LXXLL motives. This is achieved by lasofoxifene occupying the space normally filled by Leu-540's side group and modulating the conformation of residues of helix 11 (His-524, Leu-525). Furthermore, lasofoxifene also directly interferes with helix 12 positioning by the drug's ethyl [[Pyrrolidine|pyrrolidine group]].<ref name=Rosano_2011 /> In vitro studies indicate that bazedoxifene competitively blocks 17β-estradiol by high and similar binding to both ERα and ERβ.<ref>{{cite book | editor-last1 = Sanchez | editor-first1 = Antonio Cano | editor-last2 = Calaf i Alsina | editor-first2 = Joaquin | editor-last3 = Dueñas-Díez | editor-first3 = José-Luis | title = Selective estrogen receptor modulators a new brand of multitarget drugs | date = 2006 | publisher = Springer | location = Berlin | isbn = 978-3-540-24227-7 | edition = 1st | pages = 282–3 | first = Santiago | last = Palacios | name-list-style = vanc | chapter = Endometrial Effects of SERMs | chapter-url = https://books.google.com/books?id=heJDAAAAQBAJ&q=bazedoxifene&pg=PA283 | doi = 10.1007/3-540-34742-9_11 }}</ref> Bazedoxifenes main binding domain consists of the 2-phenyl-3-methylindole and a hexamethylenamine ring at the side chain affected region.<ref name=Kung2009 />

Ospemifene is an oxidative deaminated metabolite of toremifene as has a similar binding to ER as toremifene and tamoxifen. The competitive binding to ERα and ERβ of the three metabolites 4-hydroxy Ospemifene, 4'-hydroxy Ospemifene and the 4-hydroxy-, side chain carboxylic acid Ospemifene is at least as high as the parent compound.<ref>{{cite web | publisher = The European Medicines Agency (EMA) | title = Senshio (ospemifene) | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002780/human_med_001837.jsp&mid=WC0b01ac058001d124 | access-date = 2015-11-02 | archive-date = 2018-06-20 | archive-url = https://web.archive.org/web/20180620173809/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002780%2Fhuman_med_001837.jsp&mid=WC0b01ac058001d124 | url-status = dead }}</ref>