MASOPROCOL

US Previously Marketed

First approved in 1992

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22O4
Molecular Weight	302.3649
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](CC1=CC=C(O)C(O)=C1)[C@H](C)CC2=CC=C(O)C(O)=C2

InChI

InChIKey=HCZKYJDFEPMADG-TXEJJXNPSA-N

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+

HIDE SMILES / InChI

Description
Sources: http://www.druglib.com/activeingredient/masoprocol/

Misoprostol is an antineoplastic drug used to treat skin growths caused by sun exposure. Masoprocol is a novel antineoplastic agent was used for the treatment of actinic keratoses (precancerous skin growths that can become malignant if left untreated). Masoprocol was withdrawn from the U.S. market in June 1996. It is not known exactly how Masoprocol works. 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. Symptoms of overdose or allergic reaction include bluish coloration of skin, dizziness, severe, or feeling faint, wheezing or trouble in breathing.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: http://www.druglib.com/activeingredient/masoprocol/	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Actinic keratosis 12 Sources: http://www.medicatione.com/?c=drug&s=masoprocol	Primary		Approved 8583	ACTINEX Approved Use Used for the treatment of actinic keratoses (precancerous skin growths that can become malignant if left untreated). Launch Date 1992

C_max

Value	Dose	Co-administered	Analyte	Population
14.7 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11318430	50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		MASOPROCOL plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
247.7 μg × min/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11318430	50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		MASOPROCOL plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
135 min EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11318430	50 mg/kg single, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		MASOPROCOL plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2500 mg 1 times / day multiple, oral Highest studied dose Dose: 2500 mg, 1 times / day Route: oral Route: multiple Dose: 2500 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18234062	unhealthy, 48-81 years Health Status: unhealthy Age Group: 48-81 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/18234062	Sources: https://pubmed.ncbi.nlm.nih.gov/18234062
10 % 2 times / day multiple, topical Dose: 10 %, 2 times / day Route: topical Route: multiple Dose: 10 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8040425	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/8040425	Other AEs: Contact dermatitis... Other AEs: Contact dermatitis (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/8040425

AEs

AE	Significance	Dose	Population
Contact dermatitis	4 patients	10 % 2 times / day multiple, topical Dose: 10 %, 2 times / day Route: topical Route: multiple Dose: 10 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8040425	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/8040425

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:73468	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:73468
ZINC	ZINC000000012342	http://zinc15.docking.org/substances/ZINC000000012342

PubMed

Title	Date	PubMed
Synthesis and anticancer activity of nordihydroguaiaretic acid (NDGA) and analogues.	2001 Dec	12375879
Nordihydroguaiaretic acid elevates osteoblastic intracellular Ca2+.	2001 Dec	11903955
Progressive apoptosis in chorion laeve trophoblast cells of human fetal membrane tissues during in vitro incubation is suppressed by antioxidative reagents.	2001 Dec	11733013
Intracellular signaling pathway of FGF-2-modulated corneal endothelial cell migration during wound healing in vitro.	2001 Nov	11747364
Lipoxygenase inhibitors inhibit heparin-releasable lipoprotein lipase activity in 3T3-L1 adipocytes and enhance body fat reduction in mice by conjugated linoleic acid.	2001 Nov 30	11750884
[Effect of exogenous leukotrienes and lipoxygenase inhibitors on apoptosis and necrosis in cultured rat hepatocytes].	2002	12125283
[Simultaneous determination of five antioxidants in food by HPLC with fluorescence detection].	2002 Apr	12092411
Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells.	2002 Apr 8	11953870
Kinetics of inhibition of leukocyte 12-lipoxygenase by the isoform-specific inhibitor 4-(2-oxapentadeca-4-yne)phenylpropanoic acid.	2002 Aug 13	12162745
Neurons overexpressing mutant presenilin-1 are more sensitive to apoptosis induced by endoplasmic reticulum-Golgi stress.	2002 Aug 15	12210846
Native LDL induces proliferation of human vascular smooth muscle cells via redox-mediated activation of ERK 1/2 mitogen-activated protein kinases.	2002 Feb	11882624
Multiple biological effects of inhibitors of arachidonic acid metabolism on human keratinocytes.	2002 Feb	11875646
5-Lipoxygenase and human pulmonary artery endothelial cell proliferation.	2002 Feb	11788406
Arachidonic and linoleic acid metabolism in mouse intestinal tissue: evidence for novel lipoxygenase activity.	2002 Feb 1	11811948
Effects of inhibitors of the lipo-oxygenase family of enzymes on the store-operated calcium current I(CRAC) in rat basophilic leukaemia cells.	2002 Feb 15	11850504
Tending tender tendons.	2002 Feb 8	11834816
Cytosolic phospholipase A2 and lipoxygenase are involved in cell cycle progression in neuroblastoma cells.	2002 Jan	11852915
The lipoxygenase pathways are involved in LH-stimulated progesterone production in bovine corpus luteum.	2002 Jan	11789897
Differential effect of brefeldin A on the palmitoylation of surfactant protein C proprotein mutants.	2002 Jan 11	11779204
[Lipoxygenase inhibitors induce rat hepatocyte apoptosis in primary culture].	2002 Jan-Feb	12199093
Evidence for the involvement of cyclooxygenase activity in the development of cocaine sensitization.	2002 Jan-Feb	11812506
Stimulatory effects of adenosine on prolactin secretion in the pituitary gland of the rat.	2002 Jul	12131928
Regulation of apoptosis through arachidonate cascade in mammalian cells.	2002 Jul-Dec	12396127
Nordihydroguaiaretic acid-mediated inhibition of ultraviolet B-induced activator protein-1 activation in human keratinocytes.	2002 Jun	12112316
Participation of the arachidonic acid cascade pathway in macrophage binding/uptake of oxidized low density lipoprotein.	2002 Jun	12081134
Structure-activity relationship studies of nordihydroguaiaretic acid inhibitors toward soybean, 12-human, and 15-human lipoxygenase.	2002 Jun 6	12036375
Effects of various reactive oxygen species on the guinea pig trachea and its epithelium.	2002 Mar	11949881
Expression and induction of the stress protein alpha-B-crystallin in vascular endothelial cells.	2002 Mar	11914917
Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in C6 glioma cells.	2002 Mar	11741008
Possible implication of Golgi-nucleating function for the centrosome.	2002 Mar 1	11855815
Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols.	2002 Mar 15	11931850
Comparative quantitative structure toxicity relationships for flavonoids evaluated in isolated rat hepatocytes and HeLa tumor cells.	2002 Mar 20	11879815
Mechanisms underlying the activation of large conductance Ca2+-activated K+ channels by nordihydroguaiaretic acid.	2002 May	12083743
Nordihydroguaiaretic acid potently breaks down pre-formed Alzheimer's beta-amyloid fibrils in vitro.	2002 May	12065652
Involvement of glycogen synthase kinase-3beta and tau phosphorylation in neuronal Golgi disassembly.	2002 May	12065646
Effects of cyclooxygenase and lipoxygenase inhibition on basal- and serotonin-induced ion transport in rat colon.	2002 May	12039683
Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of longitudinal smooth muscle from the guinea-pig distal colon in vitro.	2002 May 31	12063081
alpha 2B-adrenergic receptor activates MAPK via a pathway involving arachidonic acid metabolism, matrix metalloproteinases, and epidermal growth factor receptor transactivation.	2002 May 31	11891218
Effects of brefeldin A and nordihydroguaiaretic acid on endomembrane dynamics and lipid synthesis in plant cells.	2002 May 8	11997023
Concerted regulation of free arachidonic acid and hormone-induced steroid synthesis by acyl-CoA thioesterases and acyl-CoA synthetases in adrenal cells.	2002 Nov	12423359
Establishment of a first-order kinetic model of light chain-associated amyloid fibril extension in vitro.	2002 Nov 19	12429509
Investigation of the role of lipoxygenase in bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung.	2002 Oct	12387624
Effect of nordihydroguaiaretic acid on intracellular Ca(2+) concentrations in hepatocytes.	2002 Oct	12206814
Contribution of different phospholipases and arachidonic acid metabolites in the response of gallbladder smooth muscle to cholecystokinin.	2002 Oct 1	12234620
Bradykinin increases permeability by calcium and 5-lipoxygenase in the ECV304/C6 cell culture model of the blood-brain barrier.	2002 Oct 25	12384249
Platelet aggregating response to platelet activating factor participates in activation of the 12-lipoxygenase pathway in platelets from rabbits.	2002 Sep	12384648
N-acylethanolamines are metabolized by lipoxygenase and amidohydrolase in competing pathways during cottonseed imbibition.	2002 Sep	12226518
Design, synthesis, and biological evaluation of a cephalosporin-monohydroguaiaretic acid prodrug activated by a monoclonal antibody-beta-lactamase conjugate.	2002 Sep	12110314
Inhibition of peroxisome proliferator-activated receptor (PPAR)-mediated keratinocyte differentiation by lipoxygenase inhibitors.	2002 Sep 15	12069687
Effect of nordihydroguaiaretic acid on the secretion of lipoprotein lipase.	2002 Sep 30	12359096

Patents

Sample Use Guides

In Vivo Use Guide

Apply to lesions b.i.d. for 14–28 d

Route of Administration: Topical

In Vitro Use Guide

Incubation of masoprocol (50 uM) with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol.

Name

Type

Language

MASOPROCOL

Official Name

English

NORDIHYDROGUAIARETIC ACID

Preferred Name

English

INSM18

Common Name

English

MESO-4,4'-(2,3-DIMETHYLTETRAMETHYLENE)DIPYROCATECHOL

Common Name

English

MASOPROCOL [MART.]

Common Name

English

NORDIHYDROGUIARETIC ACID

Common Name

English

ACTINEX

Brand Name

English

1,2-BENZENEDIOL, 4,4'-(2,3-DIMETHYL-1,4-BUTANEDIYL)BIS-, (R*,S*)-

Common Name

English

NSC-4291

Code

English

Masoprocol [WHO-DD]

Common Name

English

NORDIHYDROGUAIARETIC ACID [MI]

Common Name

English

INSM-18

Common Name

English

ORISTAR NHGA

Brand Name

English

DIHYDRONORGUAIARETIC ACID

Common Name

English

MESO-NDGA

Code

English

NDGA

Common Name

English

CHX-100

Code

English

NSC-682984

Code

English

MASOPROCOL [VANDF]

Common Name

English

Nordihydroguaiaretic Acid [WHO-DD]

Common Name

English

MASOPROCOL [USAN]

Common Name

English

4-((2R,3S)-4-(3,4-DIHYDROXYPHENYL)-2,3-DIMETHYLBUTYL)BENZENE-1,2-DIOL

Systematic Name

English

masoprocol [INN]

Common Name

English

MESO-NORDIHYDROGUAIARETIC ACID

Common Name

English

NORDIHYDROGUAIARETATE

Common Name

English

1,2-BENZENEDIOL, 4,4'-((2R,3S)-2,3-DIMETHYL-1,4-BUTANEDIYL)BIS-, REL-

Systematic Name

English

MASOPROCOL [ORANGE BOOK]

Common Name

English

DINORGUAIARETIC ACID, DIHYDRO-

Common Name

English

1,2-BENZENEDIOL, 4,4'-(2,3-DIMETHYL-1,4-BUTANEDIYL)BIS-

Systematic Name

English

1,4-BIS(3,4-DIHYDROXYPHENYL)-2,3-DIMETHYLBUTANE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C275