NAFENOPIN

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H22O3
Molecular Weight	310.3869
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(OC1=CC=C(C=C1)C2CCCC3=C2C=CC=C3)C(O)=O

InChI

InChIKey=XJGBDJOMWKAZJS-UHFFFAOYSA-N

InChI=1S/C20H22O3/c1-20(2,19(21)22)23-16-12-10-15(11-13-16)18-9-5-7-14-6-3-4-8-17(14)18/h3-4,6,8,10-13,18H,5,7,9H2,1-2H3,(H,21,22)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/5099889 | https://www.ncbi.nlm.nih.gov/pubmed/4577009 | https://www.ncbi.nlm.nih.gov/pubmed/2244926 | https://www.ncbi.nlm.nih.gov/pubmed/9950074

Nafenopin is a hypolipidemic drug. It is also a peroxisome proliferator. In rats and mice, nafenopin is a nongenotoxic hepatocarcinogen, which induces hepatic DNA synthesis and enzyme induction both in vivo and in hepatocyte cultures in vitro. Hepatic Ca2+ mobilization induced by nafenopin may play an important role in the mechanism by which nafenopin exerts its physiological as well as its tumour promotive activity upon chronic treatment with carcinogenic doses.

Approval Year

PubMed

Title	Date	PubMed
Peroxisome proliferation in primary cultures of rat hepatocytes.	1983 Jan	6845354
Exogenous Cu,Zn-superoxide dismutase suppresses the stimulation of neonatal rat hepatocytes' growth by tumor promoters.	1984 Dec	6333936
Effects of non-genotoxic hepatocarcinogens phenobarbital and nafenopin on phenotype and growth of different populations of altered foci in rat liver.	1989	2576472
Tumor promotion by the peroxisome proliferator nafenopin involving a specific subtype of altered foci in rat liver.	1990 Jun 15	1971196
cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor.	1993 Jun 1	7684926
Glutathione S-transferase isoenzyme patterns in different subtypes of enzyme-altered rat liver foci treated with the peroxisome proliferator nafenopin or with phenobarbital.	1993 Nov	8242872
Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin.	1994	8092930
Differential effect of peroxisome proliferators on rat glutathione S-transferase isoenzymes.	1996 Oct	8914623
Peroxisome proliferator nafenopin potentiated cytotoxicity and genotoxicity of cyclophosphamide in the liver and bone marrow cells.	1997 Jul 11	9251722
Proteomic analysis of differential protein expression in primary hepatocytes induced by EGF, tumour necrosis factor alpha or the peroxisome proliferator nafenopin.	2000 Aug	10903494
Cyclin D1 is an early target in hepatocyte proliferation induced by thyroid hormone (T3).	2001 Apr	11292661
Mouse hepatocyte response to peroxisome proliferators: dependency on hepatic nonparenchymal cells and peroxisome proliferator activated receptor alpha (PPARalpha).	2001 Aug	11570693
Proteome analysis of rat hepatomas: carcinogen-dependent tumor-associated protein variants.	2001 Aug	11565795
Nafenopin-, ciprofibroyl-, and palmitoyl-CoA conjugation in vitro: kinetic and molecular characterization of marmoset liver microsomes and expressed MLCL1.	2001 Dec 1	11716462
Peroxisome proliferators do not increase DNA synthesis in purified rat hepatocytes.	2001 Mar	11238195
Downregulation of lactoferrin by PPARalpha ligands: role in perturbation of hepatocyte proliferation and apoptosis.	2002 Aug	12151626
PPAR alpha and the regulation of cell division and apoptosis.	2002 Dec 27	12505304
Modulation by nutrients and drugs of liver acyl-CoAs analyzed by mass spectrometry.	2002 Jul	12091497
Follistatin overexpression in rodent liver tumors: a possible mechanism to overcome activin growth control.	2002 Sep	12203361
Regulation of CYP2C11 by dehydroepiandrosterone and peroxisome proliferators: identification of the negative regulatory region of the gene.	2003 Jul	12815167
Dehydroepiandrosterone affects the expression of multiple genes in rat liver including 11 beta-hydroxysteroid dehydrogenase type 1: a cDNA array analysis.	2003 Mar	12606783
Role of apoptosis for mouse liver growth regulation and tumor promotion: comparative analysis of mice with high (C3H/He) and low (C57Bl/6J) cancer susceptibility.	2004 Apr 1	15093245
trans-activation of PPARalpha and induction of PPARalpha target genes by perfluorooctane-based chemicals.	2004 Jul	15071170
[Adolescents and knowledge of sexually transmitted diseases in Tuzla Canton].	2006	16944733
Bioactivation of carboxylic acid compounds by UDP-Glucuronosyltransferases to DNA-damaging intermediates: role of glycoxidation and oxidative stress in genotoxicity.	2006 May	16696571
Suppression of peroxisomal enzyme activities and cytochrome P450 4A isozyme expression by congeneric polybrominated and polychlorinated biphenyls.	2007	18274624
Triglyceride accumulation by peroxisome proliferators in rat hepatocytes.	2007 Apr	17409492
The Role of NF-kappaB in PPARalpha-Mediated Hepatocarcinogenesis.	2008	19197377
PPAR Regulation of Inflammatory Signaling in CNS Diseases.	2008	18670616
The Role of PPARs in Cancer.	2008	18584037
The peroxisome: still a mysterious organelle.	2008 Apr	18274771
Genomic profiling reveals an alternate mechanism for hepatic tumor promotion by perfluorooctanoic acid in rainbow trout.	2008 Aug	18709148
Modulation of receptor phosphorylation contributes to activation of peroxisome proliferator activated receptor alpha by dehydroepiandrosterone and other peroxisome proliferators.	2008 Mar	18079279
A human hepatocyte-bearing mouse: an animal model to predict drug metabolism and effectiveness in humans.	2009	19884982
Proteomic study on gender differences in aging kidney of mice.	2009 Apr 9	19358702
Role of the nuclear receptors HNF4 alpha, PPAR alpha, and LXRs in the TNF alpha-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells.	2009 Dec 22	19883121
Are animal models predictive for humans?	2009 Jan 15	19146696
A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants.	2009 Nov	20049115
Regulation of CYP4A expression by bezafibrate in primary culture of rat and human hepatocytes: interspecies difference and influence of N-acetylcysteine.	2009 Oct	19647067
PRIC295, a Nuclear Receptor Coactivator, Identified from PPARα-Interacting Cofactor Complex.	2010	20885938
The Role of PPARα Activation in Liver and Muscle.	2010	20847941
Coactivators in PPAR-Regulated Gene Expression.	2010	20814439
PPARalpha: energy combustion, hypolipidemia, inflammation and cancer.	2010 Apr 16	20414453
Analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha).	2010 Jan 7	20059764
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.	2014	25058030

Patents

Sample Use Guides

In Vivo Use Guide

The repeated oral administration of nafenopin, a hypolipidaemic compound, at a dose of 100 mg/kg to male C57BL/6, DBA/2, Balb c and C3H mice caused an increase in the specific activity of liver cytosolic epoxide hydrolase, the activity of microsomal epoxide hydrolase was also increased in all except the C3H mice. In the range of 10-200 mg/kg nafenopin the induction of the two hydrolase activities was found to increase with increasing doses of the test compound.

Route of Administration: Oral

In Vitro Use Guide

Nafenopin (Ki 430 uM) was competitive inhibitor of rat peroxisomal palmitoyl-CoA formation suggesting that it binds at the active site and thus potentially functions as alternative substrate for the peroxisomal ligase.

Name

Type

Language

NAFENOPIN

Official Name

English

SU-13437

Code

English

PROPANOIC ACID, 2-METHYL-2-(4-(1,2,3,4-TETRAHYDRO-1-NAPHTHALENYL)PHENOXY)-

Common Name

English

NAFENOPIN [IARC]

Common Name

English

2-METHYL-2-(P-(1,2,3,4-TETRAHYDRO-1-NAPHTHYL)PHENOXY)PROPIONIC ACID

Common Name

English

nafenopin [INN]

Common Name

English

NAFENOPIN [USAN]

Common Name

English

Code System Code Type Description

MESH

D009255