Pregnenolone-Carbonitrile | CAS# 1434-54-4 | PXR Agonist

MedKoo Cat#: 564348 | Name: Pregnenolone-Carbonitrile

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Pregnenolone-carbonitrile is an agonist of the rodent pregnane X receptor (PXR), inducing cytochrome P450 and hepatic steatosis. Pregnenolone-Carbonitrile significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice.

Chemical Structure

Pregnenolone-Carbonitrile

CAS#1434-54-4

Theoretical Analysis

MedKoo Cat#: 564348

Name: Pregnenolone-Carbonitrile

CAS#: 1434-54-4

Chemical Formula: C22H31NO2

Exact Mass: 341.2355

Molecular Weight: 341.50

Elemental Analysis: C, 77.38; H, 9.15; N, 4.10; O, 9.37

Price and Availability

Size	Price	Availability	Quantity
25mg	USD 375.00
50mg	USD 650.00
100mg	USD 850.00

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Related CAS #

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Synonym

PCN; Pregnenolone-16alpha-carbonitrile; SC4674; SC 4674; SC-4674; Pregnenolone-carbonitrile

IUPAC/Chemical Name

(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

InChi Key

VSBHRRMYCDQLJF-ZDNYCOCVSA-N

InChi Code

InChI=1S/C22H31NO2/c1-13(24)20-14(12-23)10-19-17-5-4-15-11-16(25)6-8-21(15,2)18(17)7-9-22(19,20)3/h4,14,16-20,25H,5-11H2,1-3H3/t14-,16-,17+,18-,19-,20-,21-,22-/m0/s1

SMILES Code

N#C[C@@H]1C[C@@]2([H])[C@]3([H])CC=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]2(C)[C@H]1C(C)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

Pregnenolone 16α-carbonitrile is an orally active prototypical and effective rodent-PXR activator.

In vitro activity:

In vitro, PCN (pregnenolone-16alpha-carbonitrile) directly inhibited hepatic stellate cell transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes), suggesting that PCN acts independently of the PXR. PCN inhibited the transdifferentiation of PXR-/--derived mouse hepatic stellate cells in vitro, confirming that there is also a PXR-independent antifibrogenic effect of PCN through a direct interaction with hepatic stellate cells. These data suggest that the PXR is antifibrogenic in rodents in vivo and that a PXR-independent target for PXR activators exists in hepatic stellate cells that also functions to inhibit fibrosis. Reference: Biochem J. 2005 May 1;387(Pt 3):601-8. https://pubmed.ncbi.nlm.nih.gov/15595924/

In vivo activity:

The effect of Pgp induction in rats by pregnenolone 16α-carbonitrile (PCN) (3 days, 35 mg/kg/d, p.o.) on digoxin pharmacokinetics and intestinal transport has been assessed. After intravenous or oral digoxin dosing the arterial and hepatic portal vein (oral) AUC(0-24h) were significantly reduced by PCN pre-treatment. Biliary digoxin clearance increased 2-fold following PCN treatment. PCN significantly increased net digoxin secretion (2.05- and 4.5-fold respectively) in ileum and colon but not in duodenum or jejunum. This increased secretion correlated with increased Pgp protein expression in ileum and colon. Both intestinal and biliary excretion therefore contribute to altered digoxin disposition following PCN. Reference: Pharmaceutics. 2010 Mar 15;2(1):61-77. https://pubmed.ncbi.nlm.nih.gov/27721343/

	Solvent	mg/mL	mM
Solubility
	Acetonitrile	1.0	2.93
	DMSO	33.3	97.60
	Ethanol	1.0	2.93
	Methanol	1.0	2.93

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 341.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Liu P, Jiang L, Kong W, Xie Q, Li P, Liu X, Zhang J, Liu M, Wang Z, Zhu L, Yang H, Zhou Y, Zou J, Liu X, Liu L. PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway. Acta Pharm Sin B. 2022 May;12(5):2391-2405. doi: 10.1016/j.apsb.2021.09.031. Epub 2021 Oct 16. PMID: 35646519; PMCID: PMC9136535. 2. Marek CJ, Tucker SJ, Konstantinou DK, Elrick LJ, Haefner D, Sigalas C, Murray GI, Goodwin B, Wright MC. 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. doi: 10.1042/BJ20041598. PMID: 15595924; PMCID: PMC1134989. 3. Lowes S, Haslam IS, Fihn BM, Hilgendorf C, Karlsson JE, Simmons NL, Ungell 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. doi: 10.3390/pharmaceutics2010061. PMID: 27721343; PMCID: PMC3968349. 4. Guzelian J, Barwick JL, Hunter L, Phang TL, Quattrochi LC, Guzelian PS. 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. doi: 10.1093/toxsci/kfl116. Epub 2006 Sep 22. PMID: 16997903; PMCID: PMC1636678.

In vitro protocol:

In vivo protocol:

1. Lowes S, Haslam IS, Fihn BM, Hilgendorf C, Karlsson JE, Simmons NL, Ungell 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. doi: 10.3390/pharmaceutics2010061. PMID: 27721343; PMCID: PMC3968349. 2. Guzelian J, Barwick JL, Hunter L, Phang TL, Quattrochi LC, Guzelian PS. 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. doi: 10.1093/toxsci/kfl116. Epub 2006 Sep 22. PMID: 16997903; PMCID: PMC1636678.

1: Liang HF, Yang X, Li HL, Li X, Tian JN, Su HG, Huang M, Fang JH, Bi HC. Activation of pregnane X receptor protects against cholestatic liver injury by inhibiting hepatocyte pyroptosis. Acta Pharmacol Sin. 2024 Aug 7. doi: 10.1038/s41401-024-01357-x. Epub ahead of print. PMID: 39112769. 2: Wada K, Yamaguchi T, Tanaka H, Fujisawa T. Hepatic enzyme induction and its potential effect on thyroid hormone metabolism in the metamorphosing tadpole of Xenopus laevis (African clawed frog). J Appl Toxicol. 2024 Jul 22. doi: 10.1002/jat.4672. Epub ahead of print. PMID: 39039701. 3: Yan L, Yan Y, Yang K, Chang Q, Zhang L. Metabolomics reveals dysregulated all-trans retinoic acid and polyunsaturated fatty acid metabolism contribute to PXR-induced hepatic steatosis in mice. Toxicol Lett. 2024 Jul;398:150-160. doi: 10.1016/j.toxlet.2024.07.003. Epub 2024 Jul 4. PMID: 38971454. 4: Bi G, Liang F, Wu T, Wang P, Jiang X, Hu S, Wu C, Zhou W, Guo J, Yang X, Fang JH, Chen W, Bi H. Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats. Basic Clin Pharmacol Toxicol. 2024 Aug;135(2):148-163. doi: 10.1111/bcpt.14041. Epub 2024 Jun 17. PMID: 38887973. 5: Wu T, Li L, Zhou W, Bi G, Jiang X, Guo M, Yang X, Fang J, Pang J, Fan S, Bi H. Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16α-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes- Associated Protein Activation. Drug Metab Dispos. 2024 Jun 17;52(7):597-605. doi: 10.1124/dmd.123.001604. PMID: 38697851. 6: Zhang S, Wang T, Feng Y, Li F, Qu A, Guan X, Wang H, Xu D. Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity. J Pharm Anal. 2023 Dec;13(12):1510-1525. doi: 10.1016/j.jpha.2023.07.013. Epub 2023 Jul 25. PMID: 38223454; PMCID: PMC10785155. 7: Attema B, Kummu O, Pitkänen S, Weisell J, Vuorio T, Pennanen E, Vorimo M, Rysä J, Kersten S, Levonen AL, Hakkola J. Metabolic effects of nuclear receptor activation in vivo after 28-day oral exposure to three endocrine-disrupting chemicals. Arch Toxicol. 2024 Mar;98(3):911-928. doi: 10.1007/s00204-023-03658-2. Epub 2024 Jan 5. PMID: 38182912; PMCID: PMC10861694. 8: Karpale M, Kummu O, Kärkkäinen O, Lehtonen M, Näpänkangas J, Herfurth UM, Braeuning A, Rysä J, Hakkola J. Pregnane X receptor activation remodels glucose metabolism to promote NAFLD development in obese mice. Mol Metab. 2023 Oct;76:101779. doi: 10.1016/j.molmet.2023.101779. Epub 2023 Jul 17. PMID: 37467962; PMCID: PMC10415798. 9: Ming WH, Luan ZL, Yao Y, Liu HC, Hu SY, Du CX, Zhang C, Zhao YH, Huang YZ, Sun XW, Qiao RF, Xu H, Guan YF, Zhang XY. Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling. Acta Pharmacol Sin. 2023 Oct;44(10):2075-2090. doi: 10.1038/s41401-023-01113-7. Epub 2023 Jun 21. PMID: 37344564; PMCID: PMC10545797. 10: Xuan LN, Hu ZX, Jiang ZF, Zhang C, Sun XW, Ming WH, Liu HT, Qiao RF, Shen LJ, Liu SB, Wang GY, Wen L, Luan ZL, Yin J. Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway. CNS Neurosci Ther. 2023 Nov;29(11):3460-3478. doi: 10.1111/cns.14279. Epub 2023 Jun 2. PMID: 37269088; PMCID: PMC10580351. 11: Zhang YF, Gao Y, Yang J, Jiang YM, Huang M, Fan SC, Bi HC. Long-term treatment with the mPXR agonist PCN promotes hepatomegaly and lipid accumulation without hepatocyte proliferation in mice. Acta Pharmacol Sin. 2023 Jan;44(1):169-177. doi: 10.1038/s41401-022-00925-3. Epub 2022 Jun 30. PMID: 35773338; PMCID: PMC9812978. 12: Wang Q, Song GC, Weng FY, Zou B, Jin JY, Yan DM, Tan B, Zhao J, Li Y, Qiu FR. Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms. Front Pharmacol. 2022 May 31;13:881231. doi: 10.3389/fphar.2022.881231. PMID: 35712714; PMCID: PMC9194553. 13: Liu P, Jiang L, Kong W, Xie Q, Li P, Liu X, Zhang J, Liu M, Wang Z, Zhu L, Yang H, Zhou Y, Zou J, Liu X, Liu L. PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway. Acta Pharm Sin B. 2022 May;12(5):2391-2405. doi: 10.1016/j.apsb.2021.09.031. Epub 2021 Oct 16. PMID: 35646519; PMCID: PMC9136535. 14: Kühnlenz J, Karwelat D, Steger-Hartmann T, Raschke M, Bauer S, Vural Ö, Marx U, Tinwell H, Bars R. A microfluidic thyroid-liver platform to assess chemical safety in humans. ALTEX. 2023;40(1):61-82. doi: 10.14573/altex.2108261. Epub 2022 May 9. PMID: 35536601. 15: Niu Y, Fan S, Luo Q, Chen L, Huang D, Chang W, Qin W, Shi G. Interaction of Hepatitis B Virus X Protein with the Pregnane X Receptor Enhances the Synergistic Effects of Aflatoxin B1 and Hepatitis B Virus on Promoting Hepatocarcinogenesis. J Clin Transl Hepatol. 2021 Aug 28;9(4):466-476. doi: 10.14218/JCTH.2021.00036. Epub 2021 Apr 19. PMID: 34447675; PMCID: PMC8369009. 16: Nabil H, Kummu O, Lehenkari P, Rysä J, Risteli J, Hakkola J, Hukkanen J. Rifampicin induces the bone form of alkaline phosphatase in humans. Basic Clin Pharmacol Toxicol. 2022 Jan;130 Suppl 1:81-94. doi: 10.1111/bcpt.13586. Epub 2021 May 7. PMID: 33851518. 17: Shizu R, Ishimura M, Nobusawa S, Hosaka T, Sasaki T, Kakizaki S, Yoshinari K. The influence of the long-term chemical activation of the nuclear receptor pregnane X receptor (PXR) on liver carcinogenesis in mice. Arch Toxicol. 2021 Mar;95(3):1089-1102. doi: 10.1007/s00204-020-02955-4. Epub 2021 Jan 4. PMID: 33398415. 18: Jiang Y, Yao X, Fan S, Gao Y, Zhang H, Huang M, Bi H. Lipidomic profiling reveals triacylglycerol accumulation in the liver during pregnane X receptor activation-induced hepatomegaly. J Pharm Biomed Anal. 2021 Feb 20;195:113851. doi: 10.1016/j.jpba.2020.113851. Epub 2020 Dec 17. PMID: 33387840. 19: Luan Z, Wei Y, Huo X, Sun X, Zhang C, Ming W, Luo Z, Du C, Li Y, Xu H, Lu H, Zheng F, Guan Y, Zhang X. Pregnane X receptor (PXR) protects against cisplatin- induced acute kidney injury in mice. Biochim Biophys Acta Mol Basis Dis. 2021 Mar 1;1867(3):165996. doi: 10.1016/j.bbadis.2020.165996. Epub 2020 Oct 27. Erratum in: Biochim Biophys Acta Mol Basis Dis. 2022 Feb 1;1868(2):166305. doi: 10.1016/j.bbadis.2021.166305. PMID: 33127475. 20: Okamura M, Shizu R, Abe T, Kodama S, Hosaka T, Sasaki T, Yoshinari K. PXR Functionally Interacts with NF-κB and AP-1 to Downregulate the Inflammation- Induced Expression of Chemokine CXCL2 in Mice. Cells. 2020 Oct 15;9(10):2296. doi: 10.3390/cells9102296. PMID: 33076328; PMCID: PMC7602528.