Diarylpropionitrile

Diarylpropionitrile
Clinical data
Other names	SC-4473
Identifiers
	IUPAC name 2,3-bis(4-hydroxyphenyl)propanenitrile;
CAS Number	1428-67-7 ;
PubChem CID	102614;
ChemSpider	92686;
UNII	52XWB8Q4V8;
CompTox Dashboard (EPA)	DTXSID0040387 ;
ECHA InfoCard	100.159.105
Chemical and physical data
Formula	C15H13NO2
Molar mass	239.274 g·mol−1
3D model (JSmol)	Interactive image;
	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;

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]

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.
^ Fex Svenningsen A, Wicher G, Lundqvist J, Pettersson H, Corell M, Norlin M (May 2011). "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. doi:10.1016/j.neuint.2011.01.024. PMID 21300119. S2CID 6438705.
^ 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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[1] "2,3-Bis(4-hydroxyphenyl)propionitrile". Sigmaaldrich.com. Retrieved 26 April 2022.

[PlantZeleznik2014-2] 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.

[pmid21300119-3] Fex Svenningsen A, Wicher G, Lundqvist J, Pettersson H, Corell M, Norlin M (May 2011). "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. doi:10.1016/j.neuint.2011.01.024. PMID 21300119. S2CID 6438705.

[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.

[pmid20138435-5] 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.

[pmid24631553-6] 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.

[pmid20363876-7] 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.

[pmid22122563-8] 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.

[pmid19074580-9] 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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Diarylpropionitrile

See also

References

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