Masoprocol
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Masoprocol
- DrugBank Accession Number
- DB00179
- Background
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]
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 302.3649
Monoisotopic: 302.151809192 - Chemical Formula
- C18H22O4
- 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
Pharmacology
- Indication
Used for the treatment of actinic keratoses (precancerous skin growths that can become malignant if left untreated).
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- 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 Masoprocol was withdrawn from the U.S. market in June 1996.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.
Target Actions Organism APolyunsaturated fatty acid 5-lipoxygenase inhibitorHumans AReceptor tyrosine-protein kinase erbB-2 modulatorHumans ATransient receptor potential cation channel subfamily M member 7 inhibitorHumans USex hormone-binding globulin Not Available Humans - 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
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose or allergic reaction include bluish coloration of skin, dizziness, severe, or feeling faint, wheezing or trouble in breathing.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Masoprocol is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Masoprocol is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Masoprocol is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Masoprocol is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Masoprocol is combined with Bupivacaine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Actinex
Categories
- ATC Codes
- L01XX10 — Masoprocol
- Drug Categories
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Antioxidants
- Benzene Derivatives
- Benzyl Compounds
- Biological Factors
- Catechols
- Compounds used in a research, industrial, or household setting
- Cyclooxygenase Inhibitors
- Enzyme Inhibitors
- Lignans
- Lipoxygenase Inhibitors
- Peripheral Nervous System Agents
- Phenols
- Protective Agents
- Sensory System Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Aromatic homomonocyclic compound / Benzenoid / Catechol / Dibenzylbutane lignan skeleton / Hydrocarbon derivative / Monocyclic benzene moiety / Organic oxygen compound / Organooxygen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- nordihydroguaiaretic acid (CHEBI:73468) / Lignans (C10719)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 7BO8G1BYQU
- CAS number
- 27686-84-6
- 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)-4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]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
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
- 227239
- ChEBI
- 73468
- ChEMBL
- CHEMBL313972
- ZINC
- ZINC000000012342
- Therapeutic Targets Database
- DNC001037
- PharmGKB
- PA164746493
- Guide to Pharmacology
- GtP Drug Page
- Wikipedia
- Masoprocol
- MSDS
- Download (69 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Terminated Treatment Prostate Cancer 1 somestatus stop reason just information to hide 1 Completed Treatment Head and Neck Neoplasms 1 somestatus stop reason just information to hide 1 Completed Treatment High Grade Glioma (III or IV) 1 somestatus stop reason just information to hide 1 Terminated Treatment Acute Lymphocytic Leukemia (ALL) / Acute Myeloid Leukemia / Adult T-Cell Leukemia (ATL) / Chronic Lymphocytic Leukemia / Chronic Myeloid Leukemia (CML-BP) / Chronic Myelomonocytic Leukemia / Leukemias / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide 1 Terminated Treatment Lymphoma / Refractory Solid Tumors 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Univ arizona cancer center
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 185.5 °C PhysProp logP 5.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0136 mg/mL ALOGPS logP 3.44 ALOGPS logP 4.76 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 9.21 Chemaxon pKa (Strongest Basic) -6.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 80.92 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 86.62 m3·mol-1 Chemaxon Polarizability 33.63 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.935 Blood Brain Barrier - 0.5361 Caco-2 permeable + 0.6215 P-glycoprotein substrate Substrate 0.6654 P-glycoprotein inhibitor I Non-inhibitor 0.9519 P-glycoprotein inhibitor II Non-inhibitor 0.9144 Renal organic cation transporter Non-inhibitor 0.886 CYP450 2C9 substrate Non-substrate 0.7194 CYP450 2D6 substrate Non-substrate 0.8261 CYP450 3A4 substrate Non-substrate 0.5171 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Inhibitor 0.8891 CYP450 2D6 inhibitor Inhibitor 0.8262 CYP450 2C19 inhibitor Inhibitor 0.8628 CYP450 3A4 inhibitor Non-inhibitor 0.5833 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5322 Ames test Non AMES toxic 0.9132 Carcinogenicity Non-carcinogens 0.8614 Biodegradation Not ready biodegradable 0.9632 Rat acute toxicity 2.1491 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9462 hERG inhibition (predictor II) Non-inhibitor 0.6288
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 188.7809239 predictedDarkChem Lite v0.1.0 [M-H]- 190.7654239 predictedDarkChem Lite v0.1.0 [M-H]- 191.9596239 predictedDarkChem Lite v0.1.0 [M-H]- 176.88368 predictedDeepCCS 1.0 (2019) [M+H]+ 188.6197239 predictedDarkChem Lite v0.1.0 [M+H]+ 192.3554239 predictedDarkChem Lite v0.1.0 [M+H]+ 192.1436239 predictedDarkChem Lite v0.1.0 [M+H]+ 179.24168 predictedDeepCCS 1.0 (2019) [M+Na]+ 188.1116239 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.5514239 predictedDarkChem Lite v0.1.0 [M+Na]+ 191.9265239 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.00096 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:8615788). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
- Specific Function
- arachidonate 12(S)-lipoxygenase activity
- Gene Name
- ALOX5
- Uniprot ID
- P09917
- Uniprot Name
- Polyunsaturated fatty acid 5-lipoxygenase
- Molecular Weight
- 77982.595 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Chen HC, Xie J, Zhang Z, Su LT, Yue L, Runnels LW: Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase. PLoS One. 2010 Jun 17;5(6):e11161. doi: 10.1371/journal.pone.0011161. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization
- Specific Function
- ATP binding
- Gene Name
- ERBB2
- Uniprot ID
- P04626
- Uniprot Name
- Receptor tyrosine-protein kinase erbB-2
- Molecular Weight
- 137909.27 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium (PubMed:35561741). Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. Involved in TNF-induced necroptosis downstream of MLKL by mediating calcium influx. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1)
- Specific Function
- actin binding
- Gene Name
- TRPM7
- Uniprot ID
- Q96QT4
- Uniprot Name
- Transient receptor potential cation channel subfamily M member 7
- Molecular Weight
- 212695.37 Da
References
- Chen HC, Xie J, Zhang Z, Su LT, Yue L, Runnels LW: Blockade of TRPM7 channel activity and cell death by inhibitors of 5-lipoxygenase. PLoS One. 2010 Jun 17;5(6):e11161. doi: 10.1371/journal.pone.0011161. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General 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, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration
- Specific Function
- androgen binding
- Gene Name
- SHBG
- Uniprot ID
- P04278
- Uniprot Name
- Sex hormone-binding globulin
- Molecular Weight
- 43778.755 Da
References
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:24