Diarylpropionitrileのソースを表示

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = 
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| IUPAC_name = 2,3-bis(4-hydroxyphenyl)propanenitrile
| image = Diarylpropionitrile.svg
| width = 

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<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 1428-67-7
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| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 52XWB8Q4V8
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| PubChem = 102614
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| DrugBank = 
| ChemSpiderID_Ref = 
| ChemSpiderID = 92686

<!--Chemical data-->
| C=15 | H=13 | N=1 | O=2
| smiles = C1=CC(=CC=C1CC(C#N)C2=CC=C(C=C2)O)O
| StdInChI = 1S/C15H13NO2/c16-10-13(12-3-7-15(18)8-4-12)9-11-1-5-14(17)6-2-11/h1-8,13,17-18H,9H2
| StdInChIKey = GHZHWDWADLAOIQ-UHFFFAOYSA-N
| synonyms = SC-4473
}}

'''Diarylpropionitrile''' ('''DPN'''), also known as '''2,3-bis(p-hydroxyphenyl)propionitrile''' ('''2,3-BHPPN'''), is a [[synthetic compound|synthetic]], [[nonsteroidal]], and highly [[binding selectivity|selective]] [[agonist]] of [[Estrogen receptor beta|ERβ]] ([[IC50|IC<sub>50</sub>]] = 15 nM)<ref>{{cite web|url=http://www.sigmaaldrich.com/catalog/product/sigma/h5915?lang=en&region=US|title=2,3-Bis(4-hydroxyphenyl)propionitrile|website=Sigmaaldrich.com|access-date=26 April 2022}}</ref> that is used widely in [[scientific research]] to study the function of this [[receptor (biochemistry)|receptor]].<ref name="PlantZeleznik2014">{{cite book| vauthors = Pfaus JG, Jone LS, Flanagan-Cato LM, Blaustein JD | chapter = Female Sexual Behavior| veditors = Plant TM, Zeleznik AJ |title=Knobil and Neill's Physiology of Reproduction: Two-Volume Set| chapter-url=https://books.google.com/books?id=I1ACBAAAQBAJ&pg=PA2311|date=15 November 2014|publisher=Academic Press|isbn=978-0-12-397769-4|pages=2311–}}</ref><ref name="pmid21300119">{{cite journal | vauthors = Fex Svenningsen A, Wicher G, Lundqvist J, Pettersson H, Corell M, Norlin M | title = Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism | journal = Neurochemistry International | volume = 58 | issue = 6 | pages = 620–4 | date = May 2011 | pmid = 21300119 | doi = 10.1016/j.neuint.2011.01.024 | s2cid = 6438705 }}</ref> It is 70-fold more selective for ERβ over [[estrogen receptor alpha|ERα]],<ref>{{cite book | vauthors = Hwang KA, Choi KC | chapter = Endocrine-Disrupting Chemicals with Estrogenicity Posing the Risk of Cancer Progression in Estrogen-Responsive Gene |title=Advances in Molecular Toxicology| chapter-url=https://books.google.com/books?id=NSeiBQAAQBAJ&pg=PA16|date=5 November 2015|publisher=Academic Press|isbn=978-0-12-802430-0|pages=16–}}</ref> and has 100-fold lower [[affinity (pharmacology)|affinity]] for [[GPER]] (GPR30) relative to [[estradiol]].<ref name="pmid20138435">{{cite journal | vauthors = Rossi DV, Dai Y, Thomas P, Carrasco GA, DonCarlos LL, Muma NA, Li Q | title = Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta | journal = Psychoneuroendocrinology | volume = 35 | issue = 7 | pages = 1023–33 | date = August 2010 | pmid = 20138435 | pmc = 2891004 | doi = 10.1016/j.psyneuen.2010.01.003 | url = }}</ref> DPN produces [[antidepressant]]- and [[anxiolytic]]-like effects in animals via activation of the [[endogenous]] [[oxytocin]] system.<ref name="pmid24631553">{{cite journal | vauthors = Kudwa AE, McGivern RF, Handa RJ | title = Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats | journal = Physiology & Behavior | volume = 129 | pages = 287–296 | date = April 2014 | pmid = 24631553 | pmc = 5802969 | doi = 10.1016/j.physbeh.2014.03.004 }}</ref> First reported in 2001, DPN was the first selective ERβ agonist to be discovered, and was followed by [[prinaberel]] (ERB-041, WAY-202041), [[WAY-200070]], and [[8β-VE2]] in 2004, [[ERB-196]] (WAY-202196) in 2005, and certain [[phytoestrogen]]s like [[liquiritigenin]] and [[nyasol]] (''cis''-hinokiresinol) since 2007.<ref name="pmid20363876">{{cite journal | vauthors = Deroo BJ, Buensuceso AV | title = Minireview: Estrogen receptor-beta: mechanistic insights from recent studies | journal = Molecular Endocrinology | volume = 24 | issue = 9 | pages = 1703–1714 | date = September 2010 | pmid = 20363876 | pmc = 5417404 | doi = 10.1210/me.2009-0288 | doi-access = free }}</ref>

DPN is a [[racemic]] mixture of two [[enantiomer]]s, (R)-DPN and (S)-DPN. Relative to (R)-DPN, (S)-DPN has between 3- and 7-fold higher [[affinity (pharmacology)|affinity]] for ERβ and appears to have higher [[intrinsic activity]] in activating ERβ.<ref name="pmid22122563">{{cite journal | vauthors = Carroll VM, Jeyakumar M, Carlson KE, Katzenellenbogen JA | title = Diarylpropionitrile (DPN) enantiomers: synthesis and evaluation of estrogen receptor β-selective ligands | journal = Journal of Medicinal Chemistry | volume = 55 | issue = 1 | pages = 528–537 | date = January 2012 | pmid = 22122563 | pmc = 3381613 | doi = 10.1021/jm201436k }}</ref><ref name="pmid19074580">{{cite journal | vauthors = Weiser MJ, Wu TJ, Handa RJ | title = Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R- and S-enantiomers on behavior and hormonal response to stress | journal = Endocrinology | volume = 150 | issue = 4 | pages = 1817–1825 | date = April 2009 | pmid = 19074580 | pmc = 2659273 | doi = 10.1210/en.2008-1355 }}</ref> However, both enantiomers have very high affinity, potency, selectivity for ERβ and efficaciously activate ERβ.<ref name="pmid22122563" /> In any case, it has been suggested that (S)-DPN might be the preferred enantiomer to use for [[scientific research]].<ref name="pmid22122563" />

== See also ==
* [[ERB-196]]
* [[Erteberel]]
* [[Menerba]]
* [[WAY-166818]]
* [[WAY-214156]]

== References ==
{{Reflist}}

{{Estrogen receptor modulators}}

[[Category:GPER agonists]]
[[Category:Nitriles]]
[[Category:4-Hydroxyphenyl compounds]]
[[Category:Selective ERβ agonists]]


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