Diarylpropionitrile

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]

Diarylpropionitrile
Clinical data
Other namesSC-4473
Identifiers
IUPAC name
  • 2,3-bis(4-hydroxyphenyl)propanenitrile
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.159.105
Chemical and physical data
FormulaC15H13NO2
Molar mass239.274 g·mol−1
3D model (JSmol)
SMILES
  • C1=CC(=CC=C1CC(C#N)C2=CC=C(C=C2)O)O
InChI
  • InChI=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
  • Key:GHZHWDWADLAOIQ-UHFFFAOYSA-N

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
  1. "2,3-Bis(4-hydroxyphenyl)propionitrile". Sigmaaldrich.com. Retrieved 26 April 2022.
  2. Tony M. Plant; Anthony J. Zeleznik (15 November 2014). Knobil and Neill's Physiology of Reproduction: Two-Volume Set. Academic Press. pp. 2311–. ISBN 978-0-12-397769-4.
  3. Advances in Neuroglia Research and Application: 2012 Edition. ScholarlyEditions. 26 December 2012. pp. 333–. ISBN 978-1-4649-9280-3.
  4. Advances in Molecular Toxicology. Academic Press. 5 November 2015. pp. 16–. ISBN 978-0-12-802430-0.
  5. Uterotonic Agents—Advances in Research and Application: 2012 Edition: ScholarlyBrief. ScholarlyEditions. 26 December 2012. pp. 51–. ISBN 978-1-4816-0836-7.
  6. Kudwa AE, McGivern RF, Handa RJ (2014). "Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats". Physiol. Behav. 129: 287–96. doi:10.1016/j.physbeh.2014.03.004. PMC 5802969. PMID 24631553.
  7. Deroo BJ, Buensuceso AV (2010). "Minireview: Estrogen receptor-beta: mechanistic insights from recent studies". Mol. Endocrinol. 24 (9): 1703–14. doi:10.1210/me.2009-0288. PMC 5417404. PMID 20363876.
  8. Carroll VM, Jeyakumar M, Carlson KE, Katzenellenbogen JA (2012). "Diarylpropionitrile (DPN) enantiomers: synthesis and evaluation of estrogen receptor β-selective ligands". J. Med. Chem. 55 (1): 528–37. doi:10.1021/jm201436k. PMC 3381613. PMID 22122563.
  9. Weiser MJ, Wu TJ, Handa RJ (2009). "Estrogen receptor-beta agonist diarylpropionitrile: biological activities of R- and S-enantiomers on behavior and hormonal response to stress". Endocrinology. 150 (4): 1817–25. doi:10.1210/en.2008-1355. PMC 2659273. PMID 19074580.



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