From Wikipedia, the free encyclopedia
Chemical compound
Diarylpropionitrile (DPN ), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN ), is a
synthetic ,
nonsteroidal , and highly
selective
agonist of
ERβ (
IC50 = 15 nM)
[1] that is used widely in
scientific research to study the function of this
receptor .
[2]
[3] It is 70-fold more selective for ERβ over
ERα ,
[4] and has 100-fold lower
affinity for
GPER (GPR30) relative to
estradiol .
[5] DPN produces
antidepressant - and
anxiolytic -like effects in animals via activation of the
endogenous
oxytocin system.
[6] 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
phytoestrogens like
liquiritigenin and
nyasol (cis -hinokiresinol) since 2007.
[7]
DPN is a
racemic mixture of two
enantiomers , (R)-DPN and (S)-DPN. Relative to (R)-DPN, (S)-DPN has between 3- and 7-fold higher
affinity for ERβ and appears to have higher
intrinsic activity in activating ERβ.
[8]
[9] However, both enantiomers have very high affinity, potency, selectivity for ERβ and efficaciously activate ERβ.
[8] In any case, it has been suggested that (S)-DPN might be the preferred enantiomer to use for
scientific research .
[8]
See also
References
^
"2,3-Bis(4-hydroxyphenyl)propionitrile" . Sigmaaldrich.com . Retrieved 26 April 2022 .
^ Pfaus JG, Jone LS, Flanagan-Cato LM, Blaustein JD (15 November 2014).
"Female Sexual Behavior" . In Plant TM, Zeleznik AJ (eds.). Knobil and Neill's Physiology of Reproduction: Two-Volume Set . Academic Press. pp. 2311–.
ISBN
978-0-12-397769-4 .
^
^ Hwang KA, Choi KC (5 November 2015).
"Endocrine-Disrupting Chemicals with Estrogenicity Posing the Risk of Cancer Progression in Estrogen-Responsive Gene" . Advances in Molecular Toxicology . Academic Press. pp. 16–.
ISBN
978-0-12-802430-0 .
^ Rossi DV, Dai Y, Thomas P, Carrasco GA, DonCarlos LL, Muma NA, Li Q (August 2010).
"Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta" . Psychoneuroendocrinology . 35 (7): 1023–33.
doi :
10.1016/j.psyneuen.2010.01.003 .
PMC
2891004 .
PMID
20138435 .
^ Kudwa AE, McGivern RF, Handa RJ (April 2014).
"Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats" . Physiology & Behavior . 129 : 287–296.
doi :
10.1016/j.physbeh.2014.03.004 .
PMC
5802969 .
PMID
24631553 .
^ Deroo BJ, Buensuceso AV (September 2010).
"Minireview: Estrogen receptor-beta: mechanistic insights from recent studies" . Molecular Endocrinology . 24 (9): 1703–1714.
doi :
10.1210/me.2009-0288 .
PMC
5417404 .
PMID
20363876 .
^
a
b
c Carroll VM, Jeyakumar M, Carlson KE, Katzenellenbogen JA (January 2012).
"Diarylpropionitrile (DPN) enantiomers: synthesis and evaluation of estrogen receptor β-selective ligands" . Journal of Medicinal Chemistry . 55 (1): 528–537.
doi :
10.1021/jm201436k .
PMC
3381613 .
PMID
22122563 .
^ Weiser MJ, Wu TJ, Handa RJ (April 2009).
"Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R- and S-enantiomers on behavior and hormonal response to stress" . Endocrinology . 150 (4): 1817–1825.
doi :
10.1210/en.2008-1355 .
PMC
2659273 .
PMID
19074580 .
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