Moxestrolのソースを表示

{{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
| width = 225px
| image2 = Moxestrol molecule ball.png
| width2 = 235px

<!--Clinical data-->
| tradename = Surestryl
| pregnancy_category = X (Contraindicated)
| legal_status = Rx-only
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ether]]

<!--Pharmacokinetic data-->
| 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 = 

<!--Identifiers-->
| CAS_number_Ref = 
| CAS_number = 34816-55-2
| CAS_supplemental = 
| ATC_prefix = G03
| ATC_suffix = CB04
| PubChem = 11954041
| DrugBank_Ref = 
| DrugBank = 
| ChemSpiderID_Ref = 
| ChemSpiderID = 10128336
| UNII = 6923NT44OW
| KEGG = C14757
| ChEBI = 34857
| ChEMBL = 1628161
| synonyms = R-2858, RU-2858, NSC-118191; 11β-Methoxy-17α-ethynylestradiol; 11β-MeO-EE 11β-Methoxy-17α-ethynylestra-1,3,5(10)-triene-3,17β-diol

<!--Chemical data-->
| 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)|estrogen]] medication which has been used in [[Europe]] for the treatment of [[menopausal symptoms]] and [[menstrual disorder]]s.<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 [[oral administration|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 disorder]]s.<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 (medication)|estrogen]], or an [[agonist]] of the [[estrogen receptor]]s.<ref name="LiNandi2012" /><ref name="Nunn1992" /> It is the 11β-methoxy derivative of [[ethinylestradiol]] and is one of the most [[potency (pharmacology)|potent]] estrogens known, being some 10 to 100 times more potent than [[estradiol (medication)|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 (pharmacology)|affinity]] for the [[estrogen receptor]] (ER), its negligible [[plasma protein binding|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 (K<sub>i</sub> = 0.12&nbsp;nM and 0.15&nbsp;nM, respectively), moxestrol possesses several-fold [[binding selectivity|selectivity]] for the [[estrogen receptor alpha|ERα]] (K<sub>i</sub> = 0.50&nbsp;nM) over [[estrogen receptor beta|ERβ]] (K<sub>i</sub> = 2.6&nbsp;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 (medication)|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:#eaecf0; text-align: center;" | '''Notes:''' Values are percentages (%). Reference [[ligand (biochemistry)|ligand]]s (100%) were [[progesterone (medication)|progesterone]] for the {{abbrlink|PR|progesterone receptor}}, [[testosterone (medication)|testosterone]] for the {{abbrlink|AR|androgen receptor}}, [[estradiol (medication)|{{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 [[hydrocortisone|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 [[metabolism|metabolized]] in the [[liver]].<ref name="LiNandi2012" /> Its [[biological half-life]] is 8.2&nbsp;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 compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[estradiol (medication)|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 term|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}}

{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

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