Diarylpropionitrile (DPN), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN), is a synthetic,

nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents. List of nonsteroidal steroid receptor mod ...

, and highly selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

ERβ Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...

( IC₅₀ = 15 nM) that is used widely in

scientific research The scientific method is an empirical method for acquiring knowledge that has characterized the development of science since at least the 17th century (with notable practitioners in previous centuries; see the article history of scientific m ...

to study the function of this

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

. It is 70-fold more selective for ERβ over

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

, and has 100-fold lower

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for

GPER G protein-coupled estrogen receptor 1 (GPER), also known as G protein-coupled receptor 30 (GPR30), is a protein that in humans is encoded by the ''GPER'' gene. GPER binds to and is activated by the female sex hormone estradiol and is responsible ...

(GPR30) relative to

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

. DPN produces

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

- and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

-like effects in animals via activation of the

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

oxytocin Oxytocin (Oxt or OT) is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. It plays a role in social bonding, reproduction, childbirth, and the period after childbirth. Oxytocin ...

system. First reported in 2001, DPN was the first selective ERβ agonist to be discovered, and was followed by

prinaberel Prinaberel (INN, USAN) (developmental code names ERB-041, WAY-202041) is a synthetic, nonsteroidal, and highly selective agonist of the ERβ subtype of the estrogen receptor. It is used in scientific research to elucidate the role of the ERβ r ...

(ERB-041, WAY-202041),

WAY-200070 WAY-200070 is a synthetic, nonsteroidal, highly selective agonist of ERβ. It possesses 68-fold selectivity for ERβ over ERα ( EC50 = 2 nM and 155 nM, respectively). WAY-200070 has been found to enhance serotonergic and dopaminergic neurotr ...

, and

8β-VE2 8β-VE2, or 8β-vinylestradiol, also known as 8β-vinylestra-1,3,5(10)-triene-3β,17β-diol, is a synthetic estrogen featuring an estradiol core. It is a highly potent and selective agonist of the ERβ that is used in scientific research to st ...

in 2004,

ERB-196 ERB-196, also known as WAY-202196, is a synthetic nonsteroidal estrogen that acts as a highly selective agonist of the ERβ. It possesses 78-fold selectivity for the ERβ over the ERα. The drug was under development by Wyeth for the treatment ...

(WAY-202196) in 2005, and certain

phytoestrogen A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...

s like

liquiritigenin Liquiritigenin is a flavanone that was isolated from ''Glycyrrhiza uralensis'', and is found in a variety of plants, including ''Glycyrrhiza glabra'' (licorice). It is an estrogenic compound which acts as a selective agonist of the ERβ subtype ...

and

nyasol Nyasol, also known as ''cis''-hinokiresinol or as (''Z'')-hinokiresinol, is a lignan that is found in '' Anemarrhena asphodeloides''.Kwon, J., Kondaji, G., Song, S., Kim, C., Lee, K., Kim, W. K., & Choi, Y. (2013). Synthesis of naturally occurring ...

(''cis''-hinokiresinol) since 2007. DPN is a

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

mixture of two

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

s, (R)-DPN and (S)-DPN. Relative to (R)-DPN, (S)-DPN has between 3- and 7-fold higher

for ERβ and appears to have higher

intrinsic activity Intrinsic activity (IA) and efficacy refer to the relative ability of a drug-receptor complex to produce a maximum functional response. This must be distinguished from the affinity, which is a measure of the ability of the drug to bind to its mol ...

in activating ERβ. 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

References

GPER agonists Nitriles Phenols Selective ERβ agonists {{genito-urinary-drug-stub

See also

References