Identification
- Summary
Mequinol is a topical agent used in combination with tretinoin to treat solar lentigines.
- Generic Name
- Mequinol
- DrugBank Accession Number
- DB09516
- Background
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.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Mequinol (DB09516)
- Weight
- Average: 124.1372
Monoisotopic: 124.0524295 - Chemical Formula
- C7H8O2
- Synonyms
- 4-Methoxyphenol
- Mequinol
- External IDs
- BMS-181158
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.
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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.
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- 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.
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Categories
- ATC Codes
- D11AX06 — Mequinol
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- 1-hydroxy-2-unsubstituted benzenoid / 4-alkoxyphenol / Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Ether / Hydrocarbon derivative / Methoxybenzene / Methoxyphenol / Monocyclic benzene moiety
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- phenols, methoxybenzene (CHEBI:69441)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6HT8U7K3AM
- CAS number
- 150-76-5
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- TOXNET: 4-methoxyphenol [Link]
- Drugs.com: Mequinol and Tretinoin (Topical) [Link]
- PucChem: Mequinol Fb [Link]
- ECHA: Mequinol [Link]
- External Links
- Human Metabolome Database
- HMDB0029696
- PubChem Compound
- 9015
- PubChem Substance
- 347827871
- ChemSpider
- 8665
- 15080
- ChEBI
- 69441
- ChEMBL
- CHEMBL544
- ZINC
- ZINC000000001684
- PDBe Ligand
- 4KS
- Wikipedia
- Mequinol
- PDB Entries
- 4z3g / 4z3h / 5k1m
- FDA label
- Download (155 KB)
- MSDS
- Download (54.7 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Topical - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6353029 No 2002-03-05 2020-08-24 US 
Properties
- State
- Not Available
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 36.1 mg/mL ALOGPS logP 1.31 ALOGPS logP 1.51 Chemaxon logS -0.54 ALOGPS pKa (Strongest Acidic) 9.94 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 29.46 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 34.5 m3·mol-1 Chemaxon Polarizability 12.76 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 123.983564 predictedDarkChem Lite v0.1.0 [M-H]- 124.027464 predictedDarkChem Lite v0.1.0 [M-H]- 124.055664 predictedDarkChem Lite v0.1.0 [M-H]- 122.78812 predictedDeepCCS 1.0 (2019) [M+H]+ 126.365464 predictedDarkChem Lite v0.1.0 [M+H]+ 126.234364 predictedDarkChem Lite v0.1.0 [M+H]+ 124.129064 predictedDarkChem Lite v0.1.0 [M+H]+ 126.52092 predictedDeepCCS 1.0 (2019) [M+Na]+ 124.119864 predictedDarkChem Lite v0.1.0 [M+Na]+ 124.107864 predictedDarkChem Lite v0.1.0 [M+Na]+ 124.074564 predictedDarkChem Lite v0.1.0 [M+Na]+ 135.38826 predictedDeepCCS 1.0 (2019)
Drug created at November 30, 2015 19:10 / Updated at May 21, 2021 10:21