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Identification
NameMasoprocol
Accession NumberDB00179  (APRD01084)
TypeSmall Molecule
GroupsApproved
Description

A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. [PubChem]

Structure
Thumb
Synonyms
CHX 100
CHX-100
erythro-nordihydroguaiaretic acid
Masoprocolum
meso-1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane
meso-2,3-bis(3,4-dihydroxyphenylmethyl)butane
meso-4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol
meso-4,4'-(2,3-dimethyl-1,4-butanediyl)bis(pyrocatechol)
meso-4,4'-(2,3-dimethyltetramethylene)dipyrocatechol
meso-NDGA
meso-nordihydroguaiaretic acid
meso-β,γ-dimethyl-α,δ-bis(3,4-dihydroxyphenyl)butan
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ActinexNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII7BO8G1BYQU
CAS number27686-84-6
WeightAverage: 302.3649
Monoisotopic: 302.151809192
Chemical FormulaC18H22O4
InChI KeyInChIKey=HCZKYJDFEPMADG-TXEJJXNPSA-N
InChI
InChI=1S/C18H22O4/c1-11(7-13-3-5-15(19)17(21)9-13)12(2)8-14-4-6-16(20)18(22)10-14/h3-6,9-12,19-22H,7-8H2,1-2H3/t11-,12+
IUPAC Name
4-[(2S,3R)-3-[(3,4-dihydroxyphenyl)methyl]-2-methylbutyl]benzene-1,2-diol
SMILES
C[C@@H](CC1=CC(O)=C(O)C=C1)[[email protected]](C)CC1=CC(O)=C(O)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dibenzylbutane lignans. These are lignan compounds containing a 2,3-dibenzylbutane moiety.
KingdomOrganic compounds
Super ClassLignans, neolignans and related compounds
ClassDibenzylbutane lignans
Sub ClassNot Available
Direct ParentDibenzylbutane lignans
Alternative Parents
Substituents
  • Dibenzylbutane lignan skeleton
  • Phenylpropane
  • 1,2-diphenol
  • Phenol
  • Benzenoid
  • Monocyclic benzene moiety
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed for the treatment of actinic keratoses (precancerous skin growths that can become malignant if left untreated).
PharmacodynamicsMasoprocol is a novel antineoplastic agent. It is not known exactly how masoprocol works. Laboratory experiments have shown that masoprocol prevents cells similar to the ones found in actinic keratoses from multiplying. Masoprocol was withdrawn from the U.S. market in June 1996.
Mechanism of actionAlthough the exact mechanism of action is not known, studies have shown that masoprocol is a potent 5-lipoxygenase inhibitor and has antiproliferative activity against keratinocytes in tissue culture, but the relationship between this activity and its effectiveness in actinic keratoses is unknown. Masoprocol also inhibits prostaglandins but the significance of this action is not yet known.
Related Articles
AbsorptionLess than 1%-2% is absorbed through the skin over a 4-day period following application.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose or allergic reaction include bluish coloration of skin, dizziness, severe, or feeling faint, wheezing or trouble in breathing.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.935
Blood Brain Barrier-0.5361
Caco-2 permeable+0.6215
P-glycoprotein substrateSubstrate0.6654
P-glycoprotein inhibitor INon-inhibitor0.9519
P-glycoprotein inhibitor IINon-inhibitor0.9144
Renal organic cation transporterNon-inhibitor0.886
CYP450 2C9 substrateNon-substrate0.7194
CYP450 2D6 substrateNon-substrate0.8261
CYP450 3A4 substrateNon-substrate0.5171
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8891
CYP450 2D6 inhibitorInhibitor0.8262
CYP450 2C19 inhibitorInhibitor0.8628
CYP450 3A4 inhibitorNon-inhibitor0.5833
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5322
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8614
BiodegradationNot ready biodegradable0.9632
Rat acute toxicity2.1491 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9462
hERG inhibition (predictor II)Non-inhibitor0.6288
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Univ arizona cancer center
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point185.5 °CPhysProp
logP5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0136 mg/mLALOGPS
logP3.44ALOGPS
logP4.76ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.21ChemAxon
pKa (Strongest Basic)-6.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area80.92 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity86.62 m3·mol-1ChemAxon
Polarizability33.63 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-00di-0901000000-c0d0caa2c363f17f6c94View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesL01XX10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (69 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
References
  1. Audouin C, Mestdagh N, Lassoie MA, Houssin R, Henichart JP: N-Aminoindoline derivatives as inhibitors of 5-lipoxygenase. Bioorg Med Chem Lett. 2001 Mar 26;11(6):845-8. [PubMed:11277534 ]
  2. Lambert JD, Meyers RO, Timmermann BN, Dorr RT: Pharmacokinetic analysis by high-performance liquid chromatography of intravenous nordihydroguaiaretic acid in the mouse. J Chromatogr B Biomed Sci Appl. 2001 Apr 15;754(1):85-90. [PubMed:11318430 ]
  3. Azadzoi KM, Heim VK, Tarcan T, Siroky MB: Alteration of urothelial-mediated tone in the ischemic bladder: role of eicosanoids. Neurourol Urodyn. 2004;23(3):258-64. [PubMed:15098224 ]
  4. West M, Mhatre M, Ceballos A, Floyd RA, Grammas P, Gabbita SP, Hamdheydari L, Mai T, Mou S, Pye QN, Stewart C, West S, Williamson KS, Zemlan F, Hensley K: The arachidonic acid 5-lipoxygenase inhibitor nordihydroguaiaretic acid inhibits tumor necrosis factor alpha activation of microglia and extends survival of G93A-SOD1 transgenic mice. J Neurochem. 2004 Oct;91(1):133-43. [PubMed:15379894 ]
  5. Jeon SB, Ji KA, You HJ, Kim JH, Jou I, Joe EH: Nordihydroguaiaretic acid inhibits IFN-gamma-induced STAT tyrosine phosphorylation in rat brain astrocytes. Biochem Biophys Res Commun. 2005 Mar 11;328(2):595-600. [PubMed:15694390 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible for the epoxidation of endogenous cardiac arachidonic acid pools.
Gene Name:
CYP2J2
Uniprot ID:
P51589
Molecular Weight:
57610.165 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on March 23, 2016 16:26