Mequinol

Identification

Name
Mequinol
Accession Number
DB09516
Type
Small Molecule
Groups
Approved
Description

Mequinol is a phenol used in various applications. It is used as an inhibitor for acrylic monomers and acrylonitirles, as a stabilizer for chlorinated hydrocarbons and ethyl cellulose, as an ultraviolet inhibitor, as a chemical intermediate in the manufacture of antioxidants, pharmaceuticals, plasticizers, and dyestuffs [3]. It is found as an active ingredient in topical drugs used for skin depigmentation indicated for the treatment of solar lentigines.

Structure
Thumb
Synonyms
  • 4-Methoxyphenol
External IDs
BMS-181158
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SolagéMequinol (2 %) + Tretinoin (0.01 %)SolutionTopicalGlaxosmithkline Inc2003-01-022014-03-04Canada
SolageMequinol (20 mg/1mL) + Tretinoin (0.1 mg/1mL)SolutionTopicalStiefel Laboratories, Inc.2003-01-012010-11-30Us
Categories
UNII
6HT8U7K3AM
CAS number
150-76-5
Weight
Average: 124.1372
Monoisotopic: 124.0524295
Chemical Formula
C7H8O2
InChI Key
NWVVVBRKAWDGAB-UHFFFAOYSA-N
InChI
InChI=1S/C7H8O2/c1-9-7-4-2-6(8)3-5-7/h2-5,8H,1H3
IUPAC Name
4-methoxyphenol
SMILES
COC1=CC=C(O)C=C1

Pharmacology

Indication

Mequinol is currently primarily available only as an active ingredient in combination products combined with tretinoin that are indicated for the treatment of solar lentigines and related hyperpigmented lesions resulting from chronic sun exposure [Label].

Pharmacodynamics

Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones [3]. Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation [3]. In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds [3]. Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described [3].

Mechanism of action

Solar lentigines and related hyperpigmented lesions are localized, pigmented, macular lesions of the skin, usually on the areas of the body which have been chronically exposed to sunlight [Label]. These lesions are characterized by increased numbers of active melanocytes and increased melanin production [Label].

Although the mechanism of action of mequinol is not fully elucidated [Label], when employed as an active ingredient in combination with other agents like tretinoin in skin depigmentation products, a synergy between a number of potential mechanisms is proposed.

Firstly, mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic compounds like quinones [3]. Such cytotoxic agents are subsequently capable of damaging and destroying pigment cells, which results in skin depigmentation [3] of solar lentigines or other related hyperpigmented lesions. Nevertheless, skin cells are naturally capable of protecting themselves against such cytotoxic entities by endogenous intracellular glutathione (GSH) [3]. This protection is elicited through the enzymatic action of glutathione S-transferase (GST), which is responsible for the conjugation of agents toxic to glutathione [3]. Conversely, tretinoin has been observed to serve as a potent inhibitor of mammalian GSTs and to be capable of reducing the level of intracellular GSH in various cells [3]. As a result, the combination of mequinol with tretinoin seemingly allows for a synergistic enhancement of a melanocytotoxic effect that involves the inhibition and impairment of GSH and GST cytoprotection [3].

Secondly, even though mequinol is a substrate for the enzyme tyrosinase and therefore acts as a competitive inhibitor of the formation of melanin precursors by way of tyrosinase facilitated reactions, the clinical significance of this action is unknown [Label].

Absorption

The systemic exposure to mequinol was assessed in eight healthy subjects following two weeks of twice-daily topical treatment of a tretinoin and mequinol combination product [Label]. About dose of the product corresponding to about 37.3 ug/cm^2 of mequinol was applied to the subjects' backs [Label]. The mean Cmax for mequinol was 9.92 ng/mL (range between 4.22 and 23.62 ng/mL) and the Tmax was 2 hours (range between 1 to 2 hours) [Label]. The safety of mequinol in this combination formulation is supported by the low systemic exposures of the agent in the subjects [3].

Volume of distribution

The volume of distribution is one that suggests mequinol is distributed throughout the total body water, and intracellular concentrations are not expected to vary greatly from gross measurements [6].

Protein binding

Readily accessible data regarding the protein binding of mequinol is not available.

Metabolism

Urine samples from melanoma patients treated with mequinol were analyzed and various mequinol metabolites were identified, including 3,4-dihydroxyanisole, the two o-methyl derivatives 3-hydroxy-4-methoxyanisole and 4-hydroxy-3-methoxyanisole, and even hydroquinone which may have originated at least partly from mequinol [2]. All these identified metabolites were excreted predominantly as sulphates and glucuronides - only a small portion of the substances were present in urine in an unconjugated form [2]. Ultimately, the 3,4-dihydroxyanisole is considered the most important metabolite of mequinol [2].

Route of elimination

Mequinol is predominantly renally eliminated as its metabolites [4, 2].

Half life

Mequinol demonstrated an elimination half-life of 30 to 90 minutes following intravenous infusion of 5 or 10 grams/m^2 over 3 to 5 hours in melanoma patients; similar values were reported after intra-arterial infusion [4].

Clearance

Readily accessible data regarding the clearance of mequinol is not available. The use of mequinol containing products is typically indicated for topical use.

Toxicity

If a mequinol and tretinoin combination topical product is applied excessively, some potential adverse effects like marked redness, peeling of skin, discomfort, discoloration, or hypopigmentation may occur [Label]. Such products are not indicated for oral ingestion [Label].

MSDS data reports that chronic exposure to a dose of 25 UMOL/L in humans can result in mutagenic effects like DNA inhibition in lymphocytes [MSDS].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Mequinol.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Mequinol.
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Mequinol.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Mequinol.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Mequinol.
CymarinCymarin may decrease the cardiotoxic activities of Mequinol.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Mequinol.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Mequinol.
DigoxinDigoxin may decrease the cardiotoxic activities of Mequinol.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Mequinol.
Food Interactions
Not Available

References

General References
  1. Kumar CM, Sathisha UV, Dharmesh S, Rao AG, Singh SA: Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis. Biochimie. 2011 Mar;93(3):562-9. doi: 10.1016/j.biochi.2010.11.014. Epub 2010 Dec 7. [PubMed:21144881]
  2. Pavel S, Holden JL, Riley PA: Metabolism of 4-hydroxyanisole: identification of major urinary excretory products. Pigment Cell Res. 1989 Sep-Oct;2(5):421-6. [PubMed:2587513]
  3. TOXNET: 4-methoxyphenol [Link]
  4. Drugs.com: Mequinol and Tretinoin (Topical) [Link]
  5. PucChem: Mequinol Fb [Link]
  6. ECHA: Mequinol [Link]
External Links
Human Metabolome Database
HMDB0029696
PubChem Compound
9015
PubChem Substance
347827871
ChemSpider
8665
ChEBI
69441
ChEMBL
CHEMBL544
HET
4KS
Wikipedia
Mequinol
ATC Codes
D11AX06 — Mequinol
PDB Entries
4z3g / 4z3h / 5k1m
FDA label
Download (155 KB)
MSDS
Download (54.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6353029No2000-08-242020-08-24Us

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility36.1 mg/mLALOGPS
logP1.31ALOGPS
logP1.51ChemAxon
logS-0.54ALOGPS
pKa (Strongest Acidic)9.94ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity34.5 m3·mol-1ChemAxon
Polarizability12.76 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-00du-9300000000-7365fadaa1b55aee92c0
GC-MS Spectrum - EI-BGC-MSsplash10-0ab9-3900000000-b24cf2309ebe14f7ea37
GC-MS Spectrum - EI-BGC-MSsplash10-05gi-8900000000-22bed3d3611c3a5cd0d6
GC-MS Spectrum - EI-BGC-MSsplash10-0ab9-3900000000-b406ffca43dc64f80356
GC-MS Spectrum - EI-BGC-MSsplash10-05fr-3900000000-5f100d415313d60a9ba0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-3d4bc54dec9d0d2bf71d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-1900000000-cd190cc17b12c804fb8d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0691-9200000000-f98954ef6d73d4d0fc19
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-3cb1894d95675088e7b2
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0900000000-125ba3d5d60e387415e5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-9600000000-c374964c5ebd2e35933e

Taxonomy

Description
This compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenols
Sub Class
Methoxyphenols
Direct Parent
Methoxyphenols
Alternative Parents
4-alkoxyphenols / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Hydrocarbon derivatives
Substituents
Methoxyphenol / 4-alkoxyphenol / Phenoxy compound / Methoxybenzene / Phenol ether / Anisole / 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Monocyclic benzene moiety / Ether
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, methoxybenzene (CHEBI:69441)

Drug created on November 30, 2015 12:10 / Updated on September 21, 2018 00:17