1428-67-7 Usage
Uses
Used in Pharmaceutical Research:
2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a research compound for elucidating the biological function of estrogen receptor beta (ERβ). It helps in understanding the role of ERβ in various physiological processes and its potential as a therapeutic target.
Used in Pain Management:
In the field of pain management, 2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a specific agonist for estrogen receptor beta (ERβ) with proand anti-nociceptive actions in mice. This property makes it a potential candidate for the development of novel pain management therapies.
Used in Neurological Research:
2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a research tool in the study of neurological disorders. It has been shown to regulate the expression of GluR1, 2, and 3 in rat hippocampus, which could provide insights into the role of ERβ in cognitive functions and neurological conditions.
Used in Liver Cirrhosis Treatment:
In the medical field, 2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a potential therapeutic agent for amelioration of portal hypertension in a carbon tetrachloride-induced liver cirrhosis rat model. This suggests its potential use in the treatment of liver-related conditions.
Used in Cancer Research:
2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a research compound in cancer biology, specifically in the study of androgen-independent prostate cancer cell line PC-3. It has been shown to stimulate the proliferation of these cells via a novel pathway involving ERβ-mediated activation of β-catenin, providing valuable information for the development of targeted cancer therapies.
Used in Drug Development:
In the pharmaceutical industry, 2,3-BIS(4-HYDROXYPHENYL)-PROPIONITRILE is used as a lead compound for the development of new drugs targeting estrogen receptor beta (ERβ). Its selectivity and agonist properties make it a promising candidate for the creation of novel therapeutics for various conditions, including pain management, neurological disorders, and cancer treatment.
Biological Activity
Highly potent estrogen ER β receptor agonist with a 70-fold selectivity over ER α (EC 50 values are 0.85 and 66 nM respectively). Relaxes mesenteric arteries in vitro .
Biochem/physiol Actions
2,3-Bis(4-hydroxyphenyl)-propionitrile (Diarylprepionitrile, DPN) is an ERβ-selective agonist; IC50 = 15nM. DPN protects WT and ARKO mice and significantly decreases IL-1β following LPS treatment in young adult-derived microglia. PPT (Cat. No.H6036, ERa agonist) enhances cell proliferation, while DPN inhibits it. PPT increases Bcl-2 expression, while DPN decreases it. DPN also elevates Bax expression. DPN induces a dose-dependent increase on vitellogenin synthesis. PPT and DPN are effective in dynamically, but differentially regulating intracellular calcium signaling in hippocampal neurons. DPN is more efficacious than PPT in potentiating a physiological concentration of glutamate-induced intracellular Ca2+ rise in these neurons. DPN prevents the development of prostatic hyperplasia and inflammation in testosterone-treated LuRKO mice.
References
1) Meyers et al. (2001), Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues; J. Med. Chem., 44 4230
2) Waters et al. (2009), Estrogen receptor alpha and beta specific agonists regulate expression of synaptic proteins in rat hippocampus; Brain Res., 1290 1
3) Zhang et al. (2016), Role of estrogen receptor beta selective agonist in ameliorating portal hypertension in rats with CC14-induced liver cirrhosis; World J. Gastroenterol., 22 4484
4) Lombardi et al. (2016), Estrogen receptor beta (ERβ) mediates expression of β-catenin and proliferation in prostate cancer cell line PC-3; Mol. Cell. Endocrin. 430 12
5) Harrington et al. (2003), Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation and transrepression; Mol. Cell. Endocrinol., 206 13
Check Digit Verification of cas no
The CAS Registry Mumber 1428-67-7 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,4,2 and 8 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1428-67:
(6*1)+(5*4)+(4*2)+(3*8)+(2*6)+(1*7)=77
77 % 10 = 7
So 1428-67-7 is a valid CAS Registry Number.
InChI:InChI=1/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
1428-67-7Relevant academic research and scientific papers
Synthetic method 2,3 - bis (4 - hydroxyphenyl) propionitrile
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Paragraph 0020-0050, (2021/10/27)
2 Is disclosed. 3 - Bis (4 - hydroxyphenyl) propionitrile synthesis method relates to the technical field of electrolyte additives. To the scheme, methoxybenzene acetonitrile is dissolved in an organic solvent,5 - 0 °C of sodium hydride is added,5 - 0 °C
ESTROGEN RECEPTOR LIGANDS, COMPOSITIONS AND METHODS RELATED THERETO
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, (2018/03/28)
Provided are compounds and methods for treating neurodegenerative diseases and conditions, such as multiple sclerosis, using an estrogen receptor-β ligand (ΕΡβ ligand).
Diarylpropionitrile (DPN) enantiomers: Synthesis and evaluation of estrogen receptor β-selective ligands
Carroll, Vincent M.,Jeyakumar,Carlson, Kathryn E.,Katzenellenbogen, John A.
, p. 528 - 537 (2012/03/26)
Two estrogen receptor (ER) subtypes, ERα and ERβ, mediate the actions of estrogens in diverse reproductive and nonreproductive target tissues. ER subtype-selective ligands, which bind to and activate these subtypes differentially, have proved to be useful
Estrogen receptor-β potency-selective ligands: Structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues
Meyers,Sun,Carlson,Marriner,Katzenellenbogen,Katzenellenbogen
, p. 4230 - 4251 (2007/10/03)
Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERα) and beta (ERβ), we have found that 2,3-bis(hydroxyphenyl)propionitrile (DPN) acts as an agonist on both ER subtypes, but has a 70-fold higher relative binding affinity and 170-fold higher relative potency in transcription assays with ERβ than with ERα. To investigate the ERβ affinity- and potency-selective character of this DPN further, we prepared a series of DPN analogues in which both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. We also prepared other series of DPN analogues in which the nitrile functionality was replaced with acetylene groups or polar functions, to mimic the linear geometry or polarity of the nitrile, respectively. To varying degrees, all of the analogues show preferential binding affinity for ERβ (i.e., they are ERβ affinity-selective), and many, but not all of them, are also more potent in activating transcription through ERβ than through ERα (i.e., they are ERβ potency-selective). meso-2,3-Bis(4-hydroxyphenyl)succinonitrile and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERβ affinity-selective ligands, and they have an ERβ potency selectivity that is equivalent to that of DPN. The acetylene analogues have higher binding affinities but somewhat lower selectivities than their nitrile counterparts. The polar analogues have lower affinities, and only the fluorinated polar analogues have substantial affinity selectivities. This study suggests that, in this series of ligands, the nitrile functionality is critical to ERβ selectivity because it provides the optimal combination of linear geometry and polarity. Furthermore, the addition of a second nitrile group β to the nitrile in DPN or the addition of a methyl substitutent at an ortho position on the β-aromatic ring increases the affinity and selectivity of these compounds for ERβ. These ERβ-selective compounds may prove to be valuable tools in understanding the differences in structure and biological function of ERα and ERβ.
