Diarylpropionitrile (DPN), also known as 2,3-bis(p-hydroxyphenyl)propionitrile (2,3-BHPPN), is a synthetic, nonsteroidal, and highly selective agonist of ERò (IC<sub>50</sub> = 15 nM) that is used widely in scientific research to study the function of this receptor. It is 70-fold more selective for ERò over ERñ, and has 100-fold lower affinity for GPER (GPR30) relative to estradiol. DPN produces antidepressant- and anxiolytic-like effects in animals via activation of the endogenous oxytocin system. First reported in 2001, DPN was the first selective ERò agonist to be discovered, and was followed by prinaberel (ERB-041, WAY-202041), WAY-200070, and 8ò-VE2 in 2004, ERB-196 (WAY-202196) in 2005, and certain phytoestrogens like liquiritigenin and nyasol (cis-hinokiresinol) since 2007.
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 ERò and appears to have higher intrinsic activity in activating ERò. However, both enantiomers have very high affinity, potency, selectivity for ERò and efficaciously activate ERò. In any case, it has been suggested that (S)-DPN might be the preferred enantiomer to use for scientific research.