Identification

Name
Masoprocol
Accession Number
DB00179  (APRD01084, DB05900)
Type
Small Molecule
Groups
Approved, Investigational
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
  • erythro-nordihydroguaiaretic acid
  • masoprocol
  • 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
  • Nordihydroguaiaretic acid
External IDs
CHX 100 / CHX-100 / INSM-18 / INSM18 / NSC-4291
International/Other Brands
Actinex
Categories
UNII
7BO8G1BYQU
CAS number
27686-84-6
Weight
Average: 302.3649
Monoisotopic: 302.151809192
Chemical Formula
C18H22O4
InChI Key
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)[C@H](C)CC1=CC(O)=C(O)C=C1

Pharmacology

Indication

Used for the treatment of actinic keratoses (precancerous skin growths that can become malignant if left untreated).

Pharmacodynamics

Masoprocol 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 Masoprocol was withdrawn from the U.S. market in June 1996.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 action

Although 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.

TargetActionsOrganism
AArachidonate 5-lipoxygenase
inhibitor
Human
USex hormone-binding globulinNot AvailableHuman
Absorption

Less than 1%-2% is absorbed through the skin over a 4-day period following application.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014325
KEGG Drug
D04862
KEGG Compound
C10719
PubChem Compound
71398
PubChem Substance
46508042
ChemSpider
64490
BindingDB
22372
ChEBI
73468
ChEMBL
CHEMBL313972
Therapeutic Targets Database
DNC001037
PharmGKB
PA164746493
IUPHAR
4265
Guide to Pharmacology
GtP Drug Page
Wikipedia
Masoprocol
ATC Codes
L01XX10 — Masoprocol
MSDS
Download (69 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1TerminatedTreatmentProstate Cancer1
2TerminatedTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
  • Univ arizona cancer center
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)185.5 °CPhysProp
logP5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0136 mg/mLALOGPS
logP3.44ALOGPS
logP4.76ChemAxon
logS-4.4ALOGPS
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-00di-0901000000-c0d0caa2c363f17f6c94
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTOF , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0911000000-ad449f20d75c55f665cc
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzylbutane lignans. These are lignan compounds containing a 2,3-dibenzylbutane moiety.
Kingdom
Organic compounds
Super Class
Lignans, neolignans and related compounds
Class
Dibenzylbutane lignans
Sub Class
Not Available
Direct Parent
Dibenzylbutane lignans
Alternative Parents
Phenylpropanes / Catechols / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Dibenzylbutane lignan skeleton / Phenylpropane / Catechol / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Benzenoid / Monocyclic benzene moiety / Organic oxygen compound / Hydrocarbon derivative
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
nordihydroguaiaretic acid (CHEBI:73468) / Lignans (C10719)

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
Uniprot Name
Arachidonate 5-lipoxygenase
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

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 f...
Gene Name
CYP2J2
Uniprot ID
P51589
Uniprot Name
Cytochrome P450 2J2
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:38