Moxestrol

{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = | Watchedfields = | verifiedrevid = | IUPAC_name = (8''S'',9''S'',11''S'',13''S'',14''S'',17''R'')-17-ethynyl-11-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6''H''-cyclopenta[''a'']phenanthrene-3,17-diol | image = Moxestrol_structure.svg | image_class = skin-invert-image | width = 225px | image2 = Moxestrol molecule ball.png | image_class2 = bg-transparent | width2 = 235px

| bioavailability = 33%<ref name="SalmonCoussediere1983" /> | protein_bound = Minimal<ref name="SalmonCoussediere1983" /> | metabolism = Liver<ref name="LiNandi2012" /> | elimination_half-life = 8.2 hours<ref name="SalmonCoussediere1983">{{cite journal | vauthors = Salmon J, Coussediere D, Cousty C, Raynaud JP | title = Pharmacokinetics and metabolism of moxestrol in animals--rat, dog and monkey | journal = Journal of Steroid Biochemistry | volume = 19 | issue = 2 | pages = 1223–1234 | date = August 1983 | pmid = 6887930 | doi = 10.1016/0022-4731(83)90421-1 }}</ref> | excretion =

| C=21 | H=26 | O=3 | SMILES = CC12CC(C3C(C1CCC2(C#C)O)CCC4=C3C=CC(=C4)O)OC | StdInChI = 1S/C21H26O3/c1-4-21(23)10-9-17-16-7-5-13-11-14(22)6-8-15(13)19(16)18(24-3)12-20(17,21)2/h1,6,8,11,16-19,22-23H,5,7,9-10,12H2,2-3H3/t16-,17-,18-,19+,20-,21-/m0/s1 | StdInChIKey = MTMZZIPTQITGCY-OLGWUGKESA-N }}

'''Moxestrol''', sold under the brand name '''Surestryl''', is an estrogen medication which has been used in Europe for the treatment of menopausal symptoms and menstrual disorders.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA841|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=841–}}</ref><ref name="MortonHall1999">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA186|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=186–}}</ref><ref name="LiNandi2012">{{cite book| vauthors = Li JJ, Nandi S, Li SA |title=Hormonal Carcinogenesis: Proceedings of the First International Symposium|url=https://books.google.com/books?id=oPgxBwAAQBAJ&pg=PT184|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4613-9208-8|pages=184–}}</ref><ref name="Nunn1992">{{cite book| vauthors = Nunn AD |title=Radiopharmaceuticals: Chemistry and Pharmacology|url=https://books.google.com/books?id=iWrTdGUbjzEC&pg=PA342|date=19 June 1992|publisher=CRC Press|isbn=978-0-8247-8624-3|pages=342–}}</ref><ref name="MartindaleSciences1993">{{cite book|author1=William Martindale|author2=Royal Pharmaceutical Society of Great Britain. Dept. of Pharmaceutical Sciences|title=The Extra Pharmacopoeia|url=https://books.google.com/books?id=EGZWAAAAYAAJ|year=1993|publisher=Pharmaceutical Press|isbn=978-0-85369-300-0|page=1188|quote=Moxestrol is a synthetic oestrogen with actions and uses similar to thosre described for the oestrogens in general. Moxestrol is reponed to have a prolonged duration of action. It has been given by mouth in the treatment of menopausal, postmenopausal, and menstrual symptoms. Dose have ranged from 50 to 100 μg weekly for long-term therapy to 25 to 250 μg daily for short-term use.}}</ref> It is taken by mouth.<ref name="MartindaleSciences1993" /> In addition to its use as a medication, moxestrol has been used in scientific research as a radioligand of the estrogen receptor.<ref name="pmid679210">{{cite journal | vauthors = Raynaud JP, Martin PM, Bouton MM, Ojasoo T | title = 11beta-Methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (moxestrol), a tag for estrogen receptor binding sites in human tissues | journal = Cancer Research | volume = 38 | issue = 9 | pages = 3044–3050 | date = September 1978 | pmid = 679210 | url = http://cancerres.aacrjournals.org/content/38/9/3044.long }}</ref>

==Medical uses== Moxestrol is or has been used in the treatment of menopausal symptoms and menstrual disorders.<ref name="LiNandi2012" /><ref name="MartindaleSciences1993" /> It has been used at dosages of 50 to 150 μg per week for long-term therapy to 25 to 250 μg per day for short-term therapy.<ref name="MartindaleSciences1993" />

==Pharmacology== ===Pharmacodynamics=== Moxestrol is an estrogen, or an agonist of the estrogen receptors.<ref name="LiNandi2012" /><ref name="Nunn1992" /> It is the 11β-methoxy derivative of ethinylestradiol and is one of the most potent estrogens known, being some 10 to 100 times more potent than estradiol and about 5-fold more potent than ethinylestradiol.<ref name="LiNandi2012" /><ref name="Nunn1992" /> The very high potency of moxestrol has been attributed to its high affinity for the estrogen receptor (ER), its negligible plasma binding to sex hormone binding globulin and low binding to serum albumin,<ref name="SalmonCoussediere1983" /> and its lower relative rate of metabolism.<ref name="LiNandi2012" /><ref name="Nunn1992" /> In contrast to estradiol, which has roughly the same affinity for both ERs (Ki = 0.12 nM and 0.15 nM, respectively), moxestrol possesses several-fold selectivity for the ERα (Ki = 0.50 nM) over ERβ (Ki = 2.6 nM).<ref name="pmid16452668">{{cite journal | vauthors = Lund TD, Hinds LR, Handa RJ | title = The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus | journal = The Journal of Neuroscience | volume = 26 | issue = 5 | pages = 1448–1456 | date = February 2006 | pmid = 16452668 | pmc = 6675494 | doi = 10.1523/JNEUROSCI.3777-05.2006 | doi-access = free }}</ref>

{| class="wikitable sortable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;" |+ class="nowrap" | Relative affinities (%) of moxestrol and related steroids |- ! Compound || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} || {{abbrlink|SHBG|Sex hormone-binding globulin}} || {{abbrlink|CBG|Corticosteroid binding globulin}} |- | Estradiol || 2.6 || 7.9 || 100 || 0.6 || 0.13 || 8.7 || <0.1 |- | Ethinylestradiol || 15–25 || 1–3 || 112 || 1–3 || <1 || ? || ? |- | Moxestrol (11β-MeO-{{abbr|EE|ethinylestradiol}}) || 0.8 || <0.1 || 12 || 3.2 || <0.1 || <0.2 || <0.1 |- | RU-16117 (11α-MeO-{{abbr|EE|ethinylestradiol}}) || 1–3 || <1 || 13 || <1 || <1 || ? || ? |- class="sortbottom" | colspan="8" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' Values are percentages (%). Reference ligands (100%) were progesterone for the {{abbrlink|PR|progesterone receptor}}, testosterone for the {{abbrlink|AR|androgen receptor}}, {{abbr|E2|estradiol}} for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbrlink|DHT|dihydrotestosterone}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and cortisol for {{abbrlink|CBG|Corticosteroid-binding globulin}}. '''Sources:''' <ref name="RaynaudOjasoo1979">{{cite book| vauthors = Raynaud JP, Ojasoo T, Bouton MM, Philibert D |title=Drug Design|year=1979|pages=169–214|doi=10.1016/B978-0-12-060308-4.50010-X|chapter-url=https://books.google.com/books?id=bhAlBQAAQBAJ&pg=PA169|isbn=9781483216102|chapter=Receptor Binding as a Tool in the Development of New Bioactive Steroids|series=Medicinal Chemistry: A Series of Monographs |volume=11 |publisher=Academic Press }}</ref><ref name="pmid359134">{{cite journal | vauthors = Ojasoo T, Raynaud JP | title = Unique steroid congeners for receptor studies | journal = Cancer Research | volume = 38 | issue = 11 Pt 2 | pages = 4186–4198 | date = November 1978 | pmid = 359134 | url = http://cancerres.aacrjournals.org/content/38/11_Part_2/4186.short }}</ref><ref name="pmid3695484">{{cite journal | vauthors = Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP | title = Towards the mapping of the progesterone and androgen receptors | journal = Journal of Steroid Biochemistry | volume = 27 | issue = 1–3 | pages = 255–269 | date = 1987 | pmid = 3695484 | doi = 10.1016/0022-4731(87)90317-7 }}</ref><ref name="pmid7421203">{{cite journal | vauthors = Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP | display-authors = 6 | title = Steroid hormone receptors and pharmacology | journal = Journal of Steroid Biochemistry | volume = 12 | pages = 143–157 | date = January 1980 | pmid = 7421203 | doi = 10.1016/0022-4731(80)90264-2 }}</ref> |}

===Pharmacokinetics=== The bioavailability of moxestrol is 33%.<ref name="SalmonCoussediere1983" /> Its plasma protein binding is minimal.<ref name="SalmonCoussediere1983" /> The medication is metabolized in the liver.<ref name="LiNandi2012" /> Its biological half-life is 8.2 hours.<ref name="SalmonCoussediere1983" />

==Chemistry== {{See also|List of estrogens|List of estrogen esters#Ethers of steroidal estrogens}}

Moxestrol, also known as 11β-methoxy-17α-ethynylestradiol (11β-MeO-EE) or as 11β-methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol, is a synthetic estrane steroid and a derivative of estradiol.<ref name="Elks2014" /> It is specifically a derivative of ethinylestradiol (17α-ethynylestradiol) with a methoxy group at the C11β position and a derivative of 11β-methoxyestradiol with an ethynyl group at the C17α position.<ref name="Elks2014" /> The compound is the C11β isomer or C11 epimer of RU-16117 (11α-methoxy-17α-ethynylestradiol.<ref name="KayeKaye2013">{{cite book| vauthors = Kaye AM, Kaye M |title=Development of Responsiveness to Steroid Hormones: Advances in the Biosciences|url=https://books.google.com/books?id=rtXWAgAAQBAJ&pg=PA61|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-5308-7|pages=61–}}</ref>

==Society and culture==

===Generic names=== ''Moxestrol'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.<ref name="Elks2014" /><ref name="MortonHall1999" /> It is also known by its developmental code name ''R-2858'' or ''RU-2858''.<ref name="Elks2014" /><ref name="MortonHall1999" />

===Brand names=== Moxestrol is or has been marketed under the brand name ''Surestryl''.<ref name="Elks2014" /><ref name="MortonHall1999" />

===Availability=== Moxestrol is or has been marketed in Europe.<ref name="LiNandi2012" />

== References == {{Reflist}}

Category:Abandoned drugs Category:Ethynyl compounds Category:Diols Category:Estranes Category:Estrogen ethers Category:Synthetic estrogens