Diarylpropionitrile Explained

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. In any case, it has been suggested that (S)-DPN might be the preferred enantiomer to use for scientific research.

See also

Notes and References

  1. Web site: 2,3-Bis(4-hydroxyphenyl)propionitrile. Sigmaaldrich.com. 26 April 2022.
  2. Book: Pfaus JG, Jone LS, Flanagan-Cato LM, Blaustein JD . Female Sexual Behavior. Plant TM, Zeleznik AJ . Knobil and Neill's Physiology of Reproduction: Two-Volume Set. https://books.google.com/books?id=I1ACBAAAQBAJ&pg=PA2311. 15 November 2014. Academic Press. 978-0-12-397769-4. 2311–.
  3. Fex Svenningsen A, Wicher G, Lundqvist J, Pettersson H, Corell M, Norlin M . Effects on DHEA levels by estrogen in rat astrocytes and CNS co-cultures via the regulation of CYP7B1-mediated metabolism . Neurochemistry International . 58 . 6 . 620–4 . May 2011 . 21300119 . 10.1016/j.neuint.2011.01.024 . 6438705 .
  4. Book: Hwang KA, Choi KC . Endocrine-Disrupting Chemicals with Estrogenicity Posing the Risk of Cancer Progression in Estrogen-Responsive Gene . Advances in Molecular Toxicology. https://books.google.com/books?id=NSeiBQAAQBAJ&pg=PA16. 5 November 2015. Academic Press. 978-0-12-802430-0. 16–.
  5. Rossi DV, Dai Y, Thomas P, Carrasco GA, DonCarlos LL, Muma NA, Li Q . 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 . August 2010 . 20138435 . 2891004 . 10.1016/j.psyneuen.2010.01.003 .
  6. Kudwa AE, McGivern RF, Handa RJ . 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 . April 2014 . 24631553 . 5802969 . 10.1016/j.physbeh.2014.03.004 .
  7. Deroo BJ, Buensuceso AV . Minireview: Estrogen receptor-beta: mechanistic insights from recent studies . Molecular Endocrinology . 24 . 9 . 1703–1714 . September 2010 . 20363876 . 5417404 . 10.1210/me.2009-0288 . free .
  8. Carroll VM, Jeyakumar M, Carlson KE, Katzenellenbogen JA . Diarylpropionitrile (DPN) enantiomers: synthesis and evaluation of estrogen receptor β-selective ligands . Journal of Medicinal Chemistry . 55 . 1 . 528–537 . January 2012 . 22122563 . 3381613 . 10.1021/jm201436k .
  9. Weiser MJ, Wu TJ, Handa RJ . Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R- and S-enantiomers on behavior and hormonal response to stress . Endocrinology . 150 . 4 . 1817–1825 . April 2009 . 19074580 . 2659273 . 10.1210/en.2008-1355 .

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