ISOEUGENOL, (Z)-

US Approved Allergenic Extract (1994)

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H12O2
Molecular Weight	164.2011
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(\C=C/C)=CC=C1O

InChI

InChIKey=BJIOGJUNALELMI-ARJAWSKDSA-N

InChI=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3-7,11H,1-2H3/b4-3-

HIDE SMILES / InChI

Molecular Formula	C10H12O2
Molecular Weight	164.2011
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15606655http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2011/05/WC500106362.pdf
Curator's Comment: description was created based on several sources, including: http://www.umces.edu/sites/default/files/pdfs/oraa/guidance_for_industry.pdf https://www.acs.org/content/acs/en/molecule-of-the-week/archive/i/isoeugenol.html

Clove oil is a natural product, derived from the Eugenia caryophyllata tree. Clove oil is 85 to 95% eugenol. Isoeugenol and methyleugenol make up 5 to 15% of the remaining ingredients. Isoeugenol is manufactured from eugenol by a process of isomerization. Isoeugenol have been used in foods and eugenol has been used in animal feeds. Isoeugenol is used as a fish anesthetic. The mechanism of action of isoeugenol in fish has not been determined. It is hypothesised that its effects are mediated via receptors controlling cellular ion channels in a similar way to that described for local anaesthetics. Reports of adverse reactions involving the use of isoeugenol in humans are primarily confined to incidents of contact sensitization or allergy following dermal exposure.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytosolic phospholipase A2 7 Target ID: CHEMBL3816 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21995306	Inhibitor 8504
Tyrosyl-DNA phosphodiesterase 2 4 Target ID: CHEMBL2169736 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27220325	Inhibitor 8504
Cytochrome P450 1A1 32 Target ID: CHEMBL2231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22686307	Activator 1447
aryl-hydrocarbon receptor repressor 3 Target ID: 57491.0 Gene Symbol: AHRR Sources: https://www.ncbi.nlm.nih.gov/pubmed/22686307	Activator 1447
Transient receptor potential cation channel subfamily A member 1 38 Target ID: CHEMBL6007 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18456404	Activator 1447

Conditions

Condition	Modality	Targets	Highest Phase	Product
Allergic contact dermatitis 14 Sources: http://www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM294327.pdf	Diagnostic		Approved 8583	TRUE Test Approved Use Unknown
Allergic contact dermatitis 14 Sources: http://www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM294327.pdf	Diagnostic		Approved 8583	TRUE Test Approved Use Fragrance mix is composed of eight substances, including isoeugenol (approximately 15 ug).

Doses

Dose	Population	Adverse events
2 % single, topical Highest studied dose Dose: 2 % Route: topical Route: single Dose: 2 % Sources: https://pubmed.ncbi.nlm.nih.gov/8879928/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8879928/	Other AEs: Allergic contact dermatitis... Other AEs: Allergic contact dermatitis (95%) Sources: https://pubmed.ncbi.nlm.nih.gov/8879928/

AEs

AE	Significance	Dose	Population
Allergic contact dermatitis	95%	2 % single, topical Highest studied dose Dose: 2 % Route: topical Route: single Dose: 2 % Sources: https://pubmed.ncbi.nlm.nih.gov/8879928/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8879928/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP19A1 429 CYP2C19 2057	P-gp 2052	CYP1A1 151

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 16.0	inconclusive [IC50 31.7055 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 220.0	no
CYP1A1 272	inducer 1966 Sources: https://karger.com/iaa/article-abstract/124/1-3/309/171249/Eugenol-but-Not-Isoeugenol-Induces-CYPIA1-mRNA-in?redirectedFrom=fulltext	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 315.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 7.0	yes [IC50 11.4657 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 2.0	yes [IC50 2.1876 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 10.0	yes [IC50 22.4458 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 5.0	yes [IC50 7.9641 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 306 \| 307	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/853433#section=Biological-Test-Results Page: 335.0

PubMed

Title	Date	PubMed
Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor.	2015-03-01	25617811
In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis.	2014-04	24387763
Development of a new in vitro skin sensitization assay (Epidermal Sensitization Assay; EpiSensA) using reconstructed human epidermis.	2013-12	23999411
Antifungal efficacy of some natural phenolic compounds against significant pathogenic and toxinogenic filamentous fungi.	2013-10	23800587
NCTC 2544 and IL-18 production: a tool for the identification of contact allergens.	2013-04	23063874
Development of an in vitro dendritic cell-based test for skin sensitizer identification.	2013-03-18	23445166
Differentiation of skin sensitizers from irritant chemicals by interleukin-1α and macrophage inflammatory protein-2 in murine keratinocytes.	2013-01-10	23178550
B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.	2012-03-25	22245253
Isoeugenol destabilizes IL-8 mRNA expression in THP-1 cells through induction of the negative regulator of mRNA stability tristetraprolin.	2012-02	21969073
Impact of eugenol and isoeugenol on AhR translocation, target gene expression, and proliferation in human HaCaT keratinocytes.	2012	22686307
An in vitro test to screen skin sensitizers using a stable THP-1-derived IL-8 reporter cell line, THP-G8.	2011-12	21920952
Active transport of contact allergens in human monocyte-derived dendritic cells is mediated by multidrug resistance related proteins.	2011-04-15	21284934
The intra- and inter-laboratory reproducibility and predictivity of the KeratinoSens assay to predict skin sensitizers in vitro: results of a ring-study in five laboratories.	2011-04	21195160
The mouse eugenol odorant receptor: structural and functional plasticity of a broadly tuned odorant binding pocket.	2011-02-08	21142015
Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds.	2010-09	20566472
A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells.	2010-09	20491607
Identification of PDL-1 as a novel biomarker of sensitizer exposure in dendritic-like cells.	2010-09	20488241
Isoeugenol suppression of inducible nitric oxide synthase expression is mediated by down-regulation of NF-kappaB, ERK1/2, and p38 kinase.	2007-12-08	17698059
Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells.	2007-11-01	17936526
Suppression of interleukin-2 gene expression by isoeugenol is mediated through down-regulation of NF-AT and NF-kappaB.	2007-09	17630204
Do anesthetics and sampling strategies affect transcription analysis of fish tissues?	2007-06-08	17559653
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006-11	16497524
Impact of the arylhydrocarbon receptor on eugenol- and isoeugenol-induced cell cycle arrest in human immortalized keratinocytes (HaCaT).	2006-09	16972787
An odorant derivative as an antagonist for an olfactory receptor.	2004-11	15574817
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003-10	14565775
Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens.	2001-03	11258977
Anethole blocks both early and late cellular responses transduced by tumor necrosis factor: effect on NF-kappaB, AP-1, JNK, MAPKK and apoptosis.	2000-06-08	10871845
Liquid chromatographic separation and fluorometric determination of cis- and trans-isoeugenol in perfumes, colognes, and toilet waters.	1988-07-01	3417607

Patents

Sample Use Guides

In Vivo Use Guide

Subjects were investigated by closed patch test using 8mm Finn Chambers1 on Scanpor1 tape (Epitest, Tuusula, Finland) dosed with (E)-Isoeugenol (1.0% pet.) Chambers were removed after 2 days. Reactions were read on 2 occasions over 5 days.

Route of Administration: Topical

In Vitro Use Guide

Isoeugenol in low concentrations 206 uM caused a distinct decrease in twitch response in phrenic nerve-diaphragm preparations.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:39:26 GMT 2025` Edited by `admin` on `Mon Mar 31 18:39:26 GMT 2025`
Record UNII	2A4KEV8DNH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ISOEUGENOL CIS-FORM

Preferred Name

English

ISOEUGENOL, (Z)-

Systematic Name

English

ISOEUGENOL, CIS-

Systematic Name

English

(Z)-2-METHOXY-4-(1-PROPENYL)PHENOL

Systematic Name

English

ISOEUGENOL, Z-

Systematic Name

English

ISOEUGENOL CIS-FORM [MI]

Common Name

English

(Z)-4-PROPENYLGUAIACOL

Systematic Name

English

CIS-ISOEUGENOL

Systematic Name

English

Z-ISOEUGENOL

Systematic Name

English

Code System Code Type Description

MERCK INDEX

m6486