Pregnenolone 16α-carbonitrile

Names

[ Name ]:
Pregnenolone 16α-carbonitrile

[Synonym ]:
(3S,8S,9S,10R,13S,14S,16R,17S)-17-acetyl-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-16-carbonitrile
MFCD00079212
(3β,16α)-3-Hydroxy-20-oxopregn-5-ene-16-carbonitrile
16 α-Carbonitrile, Pregnenolone
3beta-Hydroxy-20-oxo-5-pregnene-16alpha-carbonitrile
pregnenolone 16alpha-carbonitrile
pregnenolone carbonitrile
Pregn-5-ene-16-carbonitrile, 3-hydroxy-20-oxo-, (3β,16α)-
Pregnenolone 16α-carbonitrile
Pregnenolone-16alpha-carbonitrile
5-Pregnen-3beta-ol-20-one-16alpha-carbonitrile

Biological Activity

[Description]:

Pregnenolone 16α-carbonitrile is an orally active prototypical and effective rodent-PXR activator. Pregnenolone 16α-carbonitrile, a synthetic steroid, induces cytochrome P4503A expression. Pregnenolone 16α-carbonitrile exhibits increased resistance to subsequent stressful insults[1][2][3].

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Cytochrome P450

Research Areas >> Metabolic Disease

[In Vitro]

Pregnenolone 16α-carbonitrile (20 μM; 9 days) directly inhibits rat hepatic stellate cell (HSCs) transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes)[4].

[In Vivo]

Pregnenolone 16α-carbonitrile (40 mg/kg/day; i.p.; for two days) induces the expression of Cyp3a11 and Cyp2b10 at the mRNA, protein, and enzymatic levels in WT mice[1]. Pregnenolone 16α-carbonitrile (100 mg/kg; ip; single dose) induces the expression of CYP3A mRNA in adult female Sprague-Dawley rats weighing 150-200 g[2]. Pregnenolone 16α-carbonitrile (35 mg/kg; gavage; once daily for three days) increase in Pgp expression in male Sprague-Dawley rats, aged approximately 100 days and weighing 250-400 g[3]. Animal Model: WT and Pxr-/- mice[1] Dosage: 40 mg/kg Administration: IP; per day for two days Result: Induced the expression of Cyp3a11 and Cyp2b10 at the mRNA, protein, and enzymatic levels in WT mice. Had little effect on the expression of Cyp3a11 in Pxr-/- mice

[References]

[1]. Yang Xie, et al. Activation of Pregnane X Receptor Sensitizes Mice to Hemorrhagic Shock-Induced Liver Injury. Hepatology. 2019 Sep;70(3):995-1010.

[2]. Simon Lowes, et al. The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat. Pharmaceutics. 2010 Mar 15;2(1):61-77.

[3]. Jeffrey Guzelian, et al. Identification of genes controlled by the pregnane X receptor by microarray analysis of mRNAs from pregnenolone 16alpha-carbonitrile-treated rats. Toxicol Sci. 2006 Dec;94(2):379-87.

[4]. Carylyn J Marek, et al. Pregnenolone-16alpha-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms. Biochem J. 2005 May 1;387(Pt 3):601-8.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
508.5±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₂H₃₁NO₂

[ Molecular Weight ]:
341.487

[ Flash Point ]:
261.3±30.1 °C

[ Exact Mass ]:
341.235474

[ PSA ]:
61.09000

[ LogP ]:
3.22

[ Vapour Pressure ]:
0.0±3.0 mmHg at 25°C

[ Index of Refraction ]:
1.558

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
TU4536500

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Pregnane X receptor agonists impair postprandial glucose tolerance.

Clin. Pharmacol. Ther. 93(6) , 556-63, (2013)

We conducted a randomized, open, placebo-controlled crossover trial to investigate the effects of the pregnane X receptor (PXR) agonist rifampin on an oral glucose tolerance test (OGTT) in 12 healthy ...

The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers.

Toxicol. Appl. Pharmacol. 272(1) , 172-9, (2013)

The cytochrome P450 (CYP) 2 gene family is the largest and most diverse CYP gene family in vertebrates. In zebrafish, we have identified 10 genes in a new subfamily, CYP2AA, which does not show orthol...

Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.

Toxicol. Lett. 188(1) , 38-44, (2009)

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity...

Related Compounds

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